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Abstract |
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
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CD23, a receptor for immunoglobulin E, is expressed at increased levels in asthmatic and atopic individuals and has been associated with disorders characterized by chronic inflammation. Using an established murine model, we employed several complementary strategies to investigate the role of CD23 in allergic pulmonary inflammation and airway hyperresponsiveness (AHR). Specifically, these approaches included the modulation of CD23 function in vivo by administration of anti-CD23 monoclonal antibody (mAb) or Fab fragments to wild-type mice and the analysis of CD23-deficient mice. Administration of anti-CD23 mAb, but not anti-CD23 Fab fragments, produced attenuation of pulmonary inflammation, AHR, and CD8+ T-cell activation. On the basis of a model that the anti-CD23 mAb transduces, whereas the Fab fragment inhibits, CD23 signaling, these results suggest that CD23 negatively regulates pulmonary inflammation and AHR. This hypothesis is supported by our observation that CD23-deficient mice developed increased inflammation and AHR after sensitization and challenge with allergen. Together, these results indicate that CD23 negatively regulates pulmonary inflammation and airway hyperreactivity.
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Introduction |
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
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The role of inflammation in the mediation and pathogenesis of asthma has been well described (1, 2). CD23, the
low-affinity immunoglobulin (Ig) E receptor, has been
found at increased levels in asthmatic and atopic individuals, and has been implicated in other diseases characterized
by chronic inflammation (3, 4). The expression of CD23
has been shown on multiple cell types, including lymphocytes, eosinophils, macrophages, and monocytes, which
are known mediators of pulmonary inflammation and
asthma (5, 6). Several functional roles for CD23 have been
described, including T cell-dependent IgE production,
augmentation of B-cell proliferation, enhancement of antigen presentation, and mediation of T- and B-cell cognate
interactions (7). CD23 has also been linked to receptor-ligand interactions between T and B cells with effects
on the CD40-CD40L pathway and the 
2-integrins (3, 11- 13). Although the immunologic roles of CD23 are under
investigation, the importance of CD23 in the mediation of
allergic pulmonary inflammation and its function as agonist versus antagonist have not been clearly delineated.
Asthma is characterized by both pulmonary inflammation and airway hyperresponsiveness (AHR) in response to allergen. We examined the role of CD23 in the modulation of allergic pulmonary inflammation and AHR, using our previously established murine model of allergic AHR (14). Using this model, we previously demonstrated increased airway inflammation, AHR, and lymphocyte activation after sensitization and aerosol challenge with ovalbumin (OVA) allergen. In this study, the immunologic and physiologic role of CD23 in allergen-induced AHR was investigated by multiple approaches: in vivo modulation of CD23 receptor functions with anti-CD23 monoclonal antibodies (mAbs) or anti-CD23 Fab fragments, and analysis of mice with a germline deletion of CD23 using CD23 knockout (KO) mice.
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Materials and Methods |
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
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Protocol for Sensitization and Challenge
Our sensitization and challenge protocol was previously described (14). Briefly, male BALB/c mice 5 to 6 wk of age and female and male CD23-deficient (18) and wild-type C57BL/6 mice (Jackson Labs, Bar Harbor, ME) 6 to 8 wk of age were sensitized by intraperitoneal (i.p.) injection with 20 µg chicken OVA and 2 mg Al(OH)3 (Alum). On Day 7, the mice received a booster i.p. injection with 10 µg OVA and 1 mg Alum. During the 1-wk period of aerosol challenge starting on Day 16 or 17, mice were exposed to nebulized 6% OVA dissolved in sterile phosphate-buffered saline (PBS) for 22 to 25 min. OVA solution was aerosolized with an ultrasonic nebulizer (Model 5000; DeVilbiss, Somerset, PA) and directed by continuous airflow into the nebulization chamber.
Determination of Airway Resistance
One day after administration of the last aerosol challenge,
the dynamic compliance and pulmonary resistance (RL) of
each animal was measured via plethysmography in response to increasing doses (33 to 3,300 µg/kg) of intravenously administered methacholine (acetyl--methacholine
chloride; Sigma, St. Louis, MO), as previously described
(14). Baseline airway reactivity was measured and maximal RL response was determined for each dose of methacholine. The log ED200, the methacholine dose required to
cause a twofold increase in RL, was calculated by regression
analysis from the dose-response curves for each animal.
In Vivo Administration of mAbs and Fab Fragments
Anti-CD23 mAb, a rat IgG2a isotype, was purified from the supernatant of the B3B4 hybridoma cell line (generous gift from Dr. D. H. Conrad, Department of Microbiology and Immunology, Medical College of Virginia) (10, 19) grown in cell culture medium (RPMI 1640, 8% fetal calf serum, 1% penicillin/streptomycin, 1% glutamine) at 37°C, 5% CO2. Rat IgG, purified from rat serum (Sigma), was used as a control. Anti-CD23 mAb and rat Ig were purified using high-pressure liquid chromatography (BioCad Sprint Perfusion Chromatograph; Perceptive BioSystems, Framingham, MA). Proteins were solubilized and diluted in sterile PBS (pH 7.40 to 7.45) before administration. Anti-CD23 mAb cleaved of its Fc portion, anti-CD23 Fab fragments, was prepared as previously described (16, 20). The purified anti-CD23 mAb and Fab were analyzed on 12.5% polyacrylamide gel in the presence of 0.1% sodium dodecyl sulfate and detected by staining with Coomassie brilliant blue. On the first day of the OVA aerosol challenge, 100 µg anti-CD23 mAb, anti-CD23 Fab fragments, or rat Ig solubilized in PBS (1 mg/ml) was injected via the tail vein. During the remainder of the week of aerosol challenge, treatment and control mice received 100 µg of anti-CD23 mAb, anti-CD23 Fab fragments, or rat Ig, respectively, every other day via i.p. injection for a total mAb dose of 400 µg.
CD23 KO Mice/Genotyping
CD23 heterozygote KO (129/Ola × C57BL/6) were developed as previously described (18). Animals were bred in virus antibody-free facilities that were maintained in accordance with the guidelines of the Committee on Animals of Harvard Medical School. At 5 to 6 wk of age, litters underwent genotyping by polymerase chain reaction (PCR) analysis. CD23 KO homozygosity and wild-type homozygosity were determined by PCR screening with three primer probes (P1, P2, and P3; Oligos Etc., Redding Center, CT) as has been described (18). Gel electrophoresis of PCR products for combination of probes P1/P2 and P2/P3 confirmed the genotype.
Bronchoalveolar Lavage and Histologic Analysis
After completion of airway reactivity measurements and serum collection, mice underwent bronchoalveolar lavage (BAL) via the tracheal cannula inserted for lung resistance measurements as described above. The BAL samples were collected, processed, and quantified as previously described (14, 15). Slides were fixed and stained with hematoxylin and eosin (H&E) stain on an automated slide processor. Cell differentials were quantitated by light microscopy (×1,000) on the basis of morphologic criteria and staining characteristics, and were expressed as percentages by a blinded investigator. After BAL, lung tissue samples from randomly chosen mice that did not undergo lymphocyte dissection were used for histopathologic analysis as described in prior work (14, 15).
Lymphocyte Isolation and Flow Cytometry
After BAL was performed, peribronchial, paratracheal, and
perihilar lymph nodes were harvested by dissection as previously described (14). Lymphocyte cell suspensions
were prepared and stained with fluorochrome-labeled mAbs
as in prior studies (14). Phycoerythrin (PE)-conjugated anti-CD4 (L3L4), fluorescence (fluorescein isothiocyanate
[FITC])-conjugated anti-B220 (CD45R), biotinylated anti-
interleukin (IL)-2 receptor (anti-CD25; 
chain) (Pharmingen, San Diego, CA), and strepavidin red 613 (GIBCO
BRL, Grand Island, NY) were obtained commercially. Anti-CD8 mAb was purified from the 53.6 hybridoma supernatant and conjugated to Cy5 (Biological Detection Systems,
Inc., Pittsburgh, PA) (21). Flow cytometry was performed
as previously described (14, 15, 21). Sample analysis was
performed on a Coulter Epics Elite fluorescence activation cell sorter using 488-nm (FITC, PE, and R613) and
633-nm (Cy5) excitation wavelengths with detection at 525 (FITC), 590 (PE), 613 (R613), and 670 (Cy5) nm. Listmode data analysis was performed as described (14).
Serum Ig Quantitation
Enzyme-linked immunosorbent assay (ELISA) plates
(Marsh Biomedical Products, Rochester, NY) were coated
with purified antimouse IgE (2 µg/ml in 0.1 M NaHCO3,
pH 8.2) (Pharmingen) at 4°C and incubated overnight.
Plates were blocked for 2 h with 3% bovine serum albumin (BSA; Sigma) at room temperature. Subsequently, murine serum, diluted 1:20 in 1% BSA/PBS, and purified
mouse IgE
isotype standard were added and incubated
overnight at 4°C. Secondary antibody, biotin antimouse
Ig light chain (Pharmingen), diluted to 2 µg/ml in 1%
BSA/PBS, was added and plates were allowed to stand for
1 h at room temperature. Avidin-peroxidase conjugate (Sigma), diluted 1:5,000 in 1% BSA/PBS, was added to the
plates, which were incubated at room temperature for 1 h.
O-phenylenediamine dihydrochloride peroxidase substrate
tablet sets (Sigma) were prepared as per manufacturer's
instructions, and solution was added immediately before
plates were read. Plates were analyzed at 492 nm (Model
2550; Bio-Rad Labs, Richmond, VA). Plates were washed
with wash buffer, PBS/0.05% Tween (Sigma), between all steps. Murine serum IgE concentrations were determined
using the standard curve generated by data analysis of the
commercial IgE standard.
Statistical Analysis
Data analysis was performed using the JMP 3.0 statistical package (SAS Institute, Cary, NC). After Mahalanobis outlier distance analysis was performed, parametric data was analyzed with the Tukey-Kramer test and nonparametric data by the Wilcoxon/Kruskal-Wallace rank-sum test. The KO animals were analyzed using multivariate analysis. Data are reported as means ± standard error. Statistical significance was defined by P < 0.05.
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Results |
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
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CD23 Mediates AHR
We have previously shown that OVA-sensitized and -challenged mice have a significant increase in AHR relative to PBS controls (14, 15, 17). To determine the role of CD23 in AHR, we performed in vivo plethysmography on OVA-sensitized and -challenged BALB/c mice that received anti-CD23 mAb or control rat Ig during OVA aerosol challenge. The index of airway resistance, log ED200 RL, was calculated by determining the methacholine dose needed to achieve a twofold increase in RL. The log ED200 RL was significantly higher in mice treated with anti-CD23 mAb than in rat Ig-treated control mice (Figure 1a). This reflects a significant decrease in airway reactivity in mice treated with anti-CD23 mAb.
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P < 0.04 and *P < 0.03, respectively. CD23 KO-OVA: log ED200 RL = 1.82 ± 0.07; WT-OVA: log ED200 RL = 2.07 ± 0.05; CD23KO-PBS: log ED200 RL = 2.13 ± 0.08; WT-PBS: log ED200 RL = 2.21 ± 0.07.
Potential mechanisms for the CD23-mediated decrease in AHR include inhibition of a positive signal or augmentation of a negative (anti-inflammatory) signal. To examine the mechanisms by which anti-CD23 mAb decreased AHR, we analyzed the effect of removing the Fc receptor portion of the mAb, producing Fab fragments (anti-CD23 Fab). We postulated that anti-CD23 Fab fragments could not be cross-linked after binding to CD23 and would not transduce signals via the CD23 molecule. If CD23 negatively regulates pulmonary inflammation and AHR, administration of anti-CD23 Fab would not result in the reduction of AHR seen with intact anti-CD23 mAb. Consistent with our hypothesis, treatment with anti-CD23 Fab fragments did not result in attenuation of airway reactivity (Figure 1a). In other models, there is precedent for different effects with intact mAb and Fab fragments (22). Although less likely, we cannot exclude the possibility that our observations result from the failure of anti-CD23 Fab fragments to block binding of the natural ligand to CD23 or from partial inhibition of the CD23 receptor because of lower-affinity binding of Fab fragments.
To differentiate between these possibilities, we used a complementary strategy to receptor blockade by investigating CD23-deficient mice (18). In these experiments, we analyzed AHR in CD23-deficient mice and wild-type mice. Airway hyperreactivity was significantly increased in OVA-sensitized and -challenged wild-type C57BL/6 mice compared with PBS-treated control animals (Figure 1b). As in our previous studies, the C57BL/6 and Balb/c mice developed significant AHR in our model (14). Importantly, and supportive of our hypothesis that CD23 transduces a negative signal, OVA-sensitized and -challenged CD23-deficient mice had a significant increase in airway reactivity compared with wild-type mice (Figure 1b), as previously described (23). To delineate the mechanisms by which AHR may be mediated by CD23, we subsequently analyzed various parameters, including lymphocyte activation, BAL, pulmonary histology, and IgE levels.
Anti-CD23 mAb Decreases Lymphocyte Activation
Because AHR in prior work has been coupled to lymphocyte activation (14), we analyzed the effects of anti-CD23 mAb on lymphocyte subsets and activation. Thoracic lymphocytes obtained from anti-CD23 mAb and rat Ig treatment groups were phenotypically analyzed by flow cytometry (Figure 2a). Significant differences were observed in lymphocyte activation, whereas T and B lymphocyte populations were not altered (Figure 2). Activation of lymphocyte subsets was determined by expression of IL-2 receptor (IL-2R). Treatment with anti-CD23 mAb resulted in a significant decrease in IL-2R expression on CD8 T lymphocytes in comparison with control mice. In addition, there was a trend toward decreased B-cell activation in the anti-CD23 mAb treatment group.
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CD23 Mediates Pulmonary Inflammation
Analysis of BAL fluid was performed to characterize the effect of anti-CD23 mAb on the airway cellular response to OVA sensitization and challenge. Treatment with anti-CD23 mAb resulted in a significant decrease in the proportion of eosinophils without changes in the proportion of neutrophils or lymphocytes (Figure 3). Histologic specimens of lung tissue were also examined by light microscopy. Control mice sensitized and challenged with OVA and treated with rat Ig had inflammatory changes similar to those seen in humans with asthma, including goblet-cell hyperplasia and inflammatory perivascular and airway infiltrates consisting of lymphocytes, neutrophils, and eosinophils (Figure 4b). In contrast, treatment with anti-CD23 mAb resulted in marked attenuation of these allergen- induced inflammatory changes (Figure 4a). Consistent with our hypothesis that CD23 transduces a negative (anti-inflammatory) signal, the attenuation of pulmonary inflammation was not observed for anti-CD23 Fab fragments in CD23- deficient mice, or in control wild-type mice after OVA sensitization and challenge (not shown).
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CD23 Deficiency Increases Serum IgE
Given that CD23 is an alternative IgE receptor and IgE is a known mediator of allergic inflammation, we measured serum IgE levels before and after allergen challenge. We have previously shown that OVA sensitization and challenge with our protocol results in increased levels of serum IgE (15). Anti-CD23 mAb-treated mice exhibited a trend toward decreased serum IgE levels in response to OVA (Figure 5a) that paralleled the observed attenuation of AHR. Consistent with the increase in airway hyperreactivity seen in allergen-treated CD23-deficient mice, a trend toward an increase in serum IgE compared with that in wild-type control mice was also observed (Figure 5b).
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Discussion |
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
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CD23 has been shown to play a role in multiple immunologic pathways and responses (1, 2). For example, elevated levels of CD23 expression have been observed in humans with asthma (24, 25) in addition to other clinical syndromes characterized by a chronic inflammatory response (3, 11). Despite numerous human and animal studies, determination of the role of CD23 as either an immunologic agonist or antagonist has not been clearly defined. The present study was designed to address the role of CD23 in the development of AHR and pulmonary inflammation in a murine allergic model.
Our studies demonstrate that treatment of OVA-sensitized and -challenged mice with anti-CD23 mAb attenuates AHR. On the basis of the assumption that the anti-CD23 mAb cross-links the CD23 receptor and transduces a signal in vivo, these results suggest that CD23 signals are anti-inflammatory. This interpretation is supported by multiple parameters analyzed. Specifically, treatment with anti-CD23 mAb decreased pulmonary inflammation on histologic examination, and decreased BAL eosinophils, CD8+ T-cell activation, and serum IgE levels. The effect of anti-CD23 mAb treatment on the experimental parameters analyzed in our studies supports a negative signaling (anti-inflammatory) role for CD23 in this model.
In other systems, whole mAb frequently cross-link receptors and transduce signals, whereas Fab fragments block signal transduction. Therefore, we analyzed treatment with anti-CD23 Fab fragments. These results showed that anti-CD23 Fab fragments did not augment AHR in response to OVA antigen (Figure 1a). Given that Fab fragments cannot cross-link the CD23 receptor, it is unlikely that the Fab fragments would transduce a signal. Together, these results suggest that anti-CD23 mAb induces a negative signal, whereas anti-CD23 Fab fragments block CD23 signals. Precedent for these findings exists in work by other investigators with anti-CD23 mAb and other Fab analogs of surface protein molecules (26).
Limitations of in vivo administration of whole mAb or Fab fragments to study specific receptor-ligand interactions include the complexities of dosing effects, kinetics, and receptor blockade versus active signaling. To address this issue further, we analyzed the effect of germline deletion of CD23 in mice sensitized and challenged with OVA. Given reported differences in the induction of AHR based on murine strains (30), we measured OVA-induced airway reactivity in CD23-deficient and background wild-type mice. Germline deletion of CD23 resulted in increased AHR and serum IgE levels in response to OVA antigen compared with wild-type control mice consistent with earlier work (23). These results offer additional evidence for our interpretation of the anti-CD23 mAb and Fab results and further support our interpretation that CD23 has an anti-inflammatory role in our model.
Although we favor a role for CD23 in negative signaling, other interpretations for the differences between the use of anti-CD23 mAb and direct deletion of CD23 are also possible. First, as is true for all KO models, deletion of CD23 at the time of immune development may result in the selective adaptation of immunity to compensate for the absence of CD23. For example, other investigators who have analyzed immunologic pathways with mAb and germline deletion have shown differences between the effects observed in these two models (34). The strain-specific differences between the mice used in this study, BALB/c and C57BL/6 mice, which have been studied previously (31), are most likely not confounding, given that we have achieved increased airway reactivity and pulmonary inflammation in response to allergen in both strains (14, 15, 17).
To define potential pathways by which anti-CD23 mAb mediates the attenuation of allergic airway inflammation, the immunologic effects of anti-CD23 mAb were characterized by flow cytometry of thoracic lymphocytes. There was a significant decrease in activated CD8+ T cells (Figure 2). A trend toward decreased B-cell activation was also observed (Figure 2b). These observations support the hypothesis that perturbation of the CD23 receptor via anti-CD23 mAb transduces a negative or downregulating signal in our model. T lymphocytes have been well established to have an important role in the promotion of allergic inflammation (1, 2) and have been shown by immunohistochemistry to constitute the perivascular infiltrate elicited by OVA antigen in our model (14). Recent data suggests that CD8+ T cells, in addition to CD4+ T cells, may also play a critical role in the mediation of airway reactivity (35, 36). Studies in a model of AHR showed that CD8+ T cells mediated the promotion of airway reactivity and IL-5 production after allergen challenge with OVA (36). CD8+ T cells have also been demonstrated to promote IL-5 production and airway eosinophilia (35). Our data suggest that regulation of regional CD8+ T-cell activation and AHR are influenced by treatment with anti-CD23 mAb.
In addition to a decrease in AHR and pulmonary inflammation, we found a statistically significant decrease in airway eosinophilia in response to anti-CD23 mAb (Figure 3) that is consistent with prior observations (37, 38). This decrease in eosinophilia is further supported by the attenuated perivascular and airway inflammation observed in mice treated with anti-CD23 mAb (Figure 4a). To define further the role of CD23, an alternative IgE receptor, serum IgE levels were also measured. IgE is a known marker and mediator of allergic inflammation that has been shown to become elevated in response to OVA sensitization and challenge with our protocol (15). As mentioned above, CD23-deficient mice demonstrated an increase in AHR in response to OVA sensitization and challenge (Figure 1b). Consistent with this observation, there was a concomitant increase in serum IgE in CD23-deficient mice in response to OVA antigen (Figure 5b). The attenuation of AHR observed with anti-CD23 mAb was mirrored by a trend toward a decrease in serum IgE (Figure 5a). These findings further support the hypothesis that CD23 attenuates allergic inflammation, and suggest a negative regulatory role for CD23, given that anti-CD23 mAb resulted in decreased AHR and serum IgE and deficiency of CD23 resulted in the augmentation of AHR and serum IgE. Activation of CD23 may play a role in regulating the immunologic response to a given IgE level. Given that the CD23 receptor has lower affinity for IgE, it may become activated only in the setting of high levels of IgE and in that setting provide a downregulating or anti-inflammatory effect. Alterations of the CD23 receptor or its level of activation could result in abnormal responses to allergic inflammation and provide an additional target for medical therapy.
In summary, we have demonstrated decreased allergic pulmonary inflammation in response to anti-CD23 mAb in an murine model of allergic AHR. In contrast, CD23-deficient mice were shown to have an augmented AHR in response to OVA antigen. In addition, AHR was not decreased by anti-CD23 Fab fragments. Quantitation of serum IgE paralleled the airway resistance findings. Analysis of lymphocyte activation suggests that the effects of anti-CD23 mAb may be mediated by preventing activation of CD8+ T cells. Taken together, our data support a role for CD23 in the modulation of allergic pulmonary inflammation, likely mediated by negative signaling.
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Footnotes |
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Address correspondence to: Dr. Patricia W. Finn, Respiratory Div., Brigham and Women's Hospital, 75 Francis St., Boston, MA 02115.
(Received in original form January 12, 1998 and in revised form September 10, 1998).
Abbreviations: airway hyperresponsiveness, AHR; bronchoalveolar lavage, BAL; bovine serum albumin, BSA; fluorescein isothiocyanate, FITC; hematoxylin and eosin, H&E; intraperitoneal, i.p.; immunoglobulin, Ig; interleukin, IL; IL-2 receptor, IL-2R; knockout, KO; dose required to cause a 2-fold increase in RL, log ED200; monoclonal antibody, mAb; ovalbumin, OVA; phosphate-buffered saline, PBS; polymerase chain reaction, PCR; phycoerythrin, PE; pulmonary resistance, RL.Acknowledgments: The authors thank Drs. Stephen J. Galli and Ellen Gravallese for their review of the manuscript and helpful discussions. This work was supported by National Institutes of Health grants ES-06568 (P.W.F.), HL56723 (P.W.F.), and AI-31525 (D.L.P.). One author (P.W.F.) is a Career Investigator of the American Lung Association and a Lynn M. Reid Scholar in Medicine, Harvard Medical School.
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References |
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Abstract
Introduction
Materials and Methods
Results
Discussion
References
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1. Azzawi, M., B. Bradley, P. K. Jeffery, A. J. Frew, A. J. Wardlaw, G. Knowles, B. Assoufi, J. V. Collins, S. Durham, and A. B. Kay. 1990. Identification of activated T lymphocytes and eosinophila in bronchial biopsies in stable atopic asthma. Am. Rev. Respir. Dis. 142: 1407-1413 [Medline].
2. Walker, C., E. Bode, L. Boer, T. T. Hansel, K. Blaser, and J. C. Virchow Jr.. 1992. Allergic and nonallergic asthmatics have distinct patterns of T-cell activation and cytokine production in peripheral blood and bronchoalveolar lavage. Am. Rev. Respir. Dis. 146: 109-115 [Medline].
3. Plater-Zyberk, C., and J. Y. Bonnefoy. 1995. Marked amelioration of established collagen-induced arthritis by treatment with antibodies to CD23 in vivo. Nat. Med. 1: 781-785 [Medline].
4. Jung, C. M., J. C. Prinz, E. P. Rieber, and J. Ring. 1995. A reduction in allergen-induced Fc epsilon R2/CD23 expression on peripheral B cells correlates with successful hyposensitization in grass pollinosis. J. Allergy Clin. Immunol. 95: 77-87 [Medline].
5. Armitage, R. J., L. K. Goff, and P. C. Beverley. 1989. Expression and functional role of CD23 on T cells. Eur. J. Immunol. 19: 31-35 [Medline].
6. Conrad, D. H.. 1990. Fc epsilon RII/CD23: the low affinity receptor for IgE [Review]. Annu. Rev. Immunol. 8: 623-645 [Medline].
7. Bonnefoy, J. Y., J. F. Gauchat, P. Life, P. Graber, J. P. Aubry, and S. Lecoanet-Henchoz. 1995. Regulation of IgE synthesis by CD23/CD21 interaction [Review]. Int. Arch. Allergy Immunol. 107: 40-42 [Medline].
8. Bacon, K., J. F. Gauchat, J. P. Aubry, S. Pochon, P. Graber, S. Henchoz, and J. Y. Bonnefoy. 1993. CD21 expressed on basophilic cells is involved in histamine release triggered by CD23 and anti-CD21 antibodies. Eur. J. Immunol. 23: 2721-2724 [Medline].
9. Aubry, J. P., S. Pochon, P. Graber, K. U. Jansen, and J. Y. Bonnefoy. 1992. CD21 is a ligand for CD23 and regulates IgE production. Nature 358: 505-507 [Medline].
10.
Kehry, M. R., and
L. C. Yamashita.
1989.
Low-affinity IgE receptor (CD23)
function on mouse B cells: role in IgE-dependent antigen focusing.
Proc.
Natl. Acad. Sci. USA
86:
7556-7560
11. Paterson, R. L. K., G. Lack, J. M. Domenico, G. Delespesse, D. Y. M. Leung, T. H. Finkel, and E. W. Gelfand. 1996. Triggering through CD40 promotes interleukin-4-induced CD23 production and enhanced soluble CD23 release in atopic disease. Eur. J. Immunol. 26: 1979-1984 [Medline].
12. Paul-Eugene, N., D. Mossalayi, M. Sarfati, K. Yamaoka, J. P. Aubry, J. Y. Bonnefoy, B. Dugas, and J. P. Kolb. 1995. Evidence for a role of Fc epsilon RII/CD23 in the IL-4-induced nitric oxide production by normal human mononuclear phagocytes. Cell. Immunol. 163: 314-318 [Medline].
13. Maliszewski, C. R., K. Grabstein, W. C. Fanslow, R. Armitage, M. K. Spriggs, and T. A. Sato. 1993. Recombinant CD40 ligand stimulation of murine B cell growth and differentiation: cooperative effects of cytokines. Eur. J. Immunol. 23: 1044-1049 [Medline].
14. Krinzman, S. J., G. T. De Sanctis, M. Cernadas, L. Kobzik, J. A. Listman, D. C. Christiani, D. L. Perkins, and P. W. Finn. 1996. T cell activation in a murine model of asthma. Am. J. Physiol. 271: L473-L481 .
15. Krinzman, S. J., G. T. De Sanctis, M. Cernadas, D. Mark, Y. Wang, J. Listman, L. Kobzik, P. L. Linsley, D. C. Christiani, D. L. Perkins, and P. W. Finn. 1996. Inhibition of T cell costimulation abrogates airway hyperresponsiveness in a murine model. J. Clin. Invest. 98: 2693-2699 [Medline].
16.
Mark, D. A.,
C. E. Donovan,
S. J. Krinzman,
L. Kobzik,
G. T. DeSanctis,
D. L. Perkins, and
P. W. Finn.
1998.
Both CD80 and CD86 costimulatory
molecules inhibit allergic pulmonary inflammation.
Int. Immunol.
10:
1647-1655
17.
DeSanctis, G. T.,
W. W. Wolyneic,
F. H. Y. Greens,
S. Qin,
A. Jiao,
P. Finn,
T. Noonan,
A. A. Joetham,
E. Gelfand,
C. M. Doerschuk, and
J. M. Drazen.
1997.
Reduction of allergic airway responses in P-selectin deficient
mice.
J. Appl. Physiol
83:
681-687
18.
Fujiwara, H.,
H. Kikutani,
S. Suematsu,
T. Naka,
K. Yoshida,
K. Yoshida,
T. Tanaka,
M. Suemura,
N. Matsumoto,
S. Kojima,
T. Kishimoto, and
N. Yoshida.
1994.
The absence of IgE antibody-mediated augmentation of
immune responses in CD23-deficient mice.
Proc. Natl. Acad. Sci. USA
91:
6835-6839
19.
Squire, C. M.,
E. J. Studer,
A. Lees,
F. D. Finkelman, and
D. H. Conrad.
1994.
Antigen presentation is enhanced by targeting antigen to the Fc
RII
by antigen-anti-Fc RII conjugates.
J. Immunol.
152:
4388-4396
[Abstract].
20. Parham, P.. 1983. On the fragmentation of monoclonal IgG1, IgG2a, and IgG2b from BALB/c mice. J. Immunol. 131: 2895-2902 [Abstract].
21. Perkins, D. L., J. A. Listman, A. Marshak-Rothstein, W. Kozlow, V. R. Kelley, P. W. Finn, and I. J. Rimm. 1996. Restriction of the TCR repertoire inhibits the development of memory T cells and prevents autoimmunity in lpr mice. J. Immunol. 156: 4961-4968 [Abstract].
22. Miller, S. D., C. L. Vanderlugt, D. J. Lenschow, J. G. Pope, N. J. Karandikar, M. C. Dal, Canto, and J. A. Bluestone. 1995. Blockade of CD28/B7-1 interactions prevents epitope spreading and clinical relapses of murine EAE. Immunity 3: 739-745 [Medline].
23.
Haczku, A.,
K. Takeda,
E. Hamelmann,
A. Oshiba,
J. Loader,
A. Joetham,
C. Irvin,
H. Kikutani, and
E. W. Gelfand.
1997.
CD23 deficient mice develop allergic airway hyperresponsiveness following sensitization with
ovalbumin.
Am. J. Respir. Crit. Care Med
156:
1945-1955
24. Gagro, A., and S. Rabatic. 1994. Allergen-induced CD23 on CD4+ T lymphocytes and CD21 on B lymphocytes in patients with allergic asthma: evidence and regulation. Eur. J. Immunol. 24: 1109-1114 [Medline].
25. Aberle, N., A. Gagro, S. Rabatic, Z. Reiner-Banovac, and D. Dekaris. 1997. Expression of CD23 antigen and its ligands in children with intrinsic and extrinsic asthma. Allergy 52: 1238-1242 [Medline].
26.
Lenschow, D. J.,
S. C. Ho,
H. Sattar,
L. Rhee,
G. Gray,
N. Nabavi,
K. C. Herold, and
J. A. Bluestone.
1995.
Differential effects of anti-B7-1 and
anti-B7-2 MAb treatment on the development of diabetes in the NOD
mouse.
J. Exp. Med.
181:
1145-1155
27. Kuchroo, V. K., M. P. Das, J. A. Brown, A. M. Ranger, S. S. Zamvil, R. A. Sobel, H. L. Weiner, N. Nabavi, and L. H. Glimcher. 1995. B7-1 and B7-2 costimulatory molecules differentially activate the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell 80: 707-718 [Medline].
28. Dugas, N., I. Vouldoukis, P. Becherel, M. Arock, P. Debre, M. Tardieu, D. M. Mossalayi, J. F. Delfraissy, J. P. Kolb, and B. Dugas. 1996. Triggering of CD23b antigen by anti-CD23 monoclonal antibodies induces interleukin-10 production by human macrophages. Eur. J. Immunol. 26: 1394-1398 [Medline].
29. Luo, H., H. Hofstetter, J. Banchereau, and G. Delespesse. 1990. Cross-linking of CD23 antigen by its natural ligand (IgE) or by anti-CD23 antibody prevents B lymphocyte proliferation and differentiation. J. Immunol. 146: 2122-2127 [Abstract].
30. De Sanctis, G. T., D. R. Merchant, D. R. Beier, R. D. Dredge, J. K. Grobholz, T. R. Martin, E. S. Lander, and J. M. Drazen. 1995. Quantitative locus analysis of airway hyperresponsiveness in A/J and C57BL/6J mice. Nat. Genet. 11: 150-154 [Medline].
31.
Corry, D. B.,
H. G. Folkesson,
M. L. Warnock,
D. J. Erle,
M. A. Matthay,
J. P. Wiener-Kronish, and
R. M. Locksley.
1996.
Interleukin 4, but not interleukin 5 or eosinophils, is required in a murine model of acute airway
hyperresponsiveness.
J. Exp. Med.
183:
109-117
32. Zhang, Y., W. J. E. Lamm, R. K. Albert, E. Y. Chi, W. R. Henderson Jr., and D. B. Lewis. 1997. Influence of the route of allergen administration and genetic background on the murine allergic pulmonary response. Am. J. Respir. Crit. Care Med. 155: 661-669 [Abstract].
33.
Foster, P. S.,
S. P. Hogan,
A. J. Ramsay,
K. I. Matthaei, and
I. G. Young.
1996.
Interleukin 5 deficiency abolishes eosinophilia, airways hyperreactivity, and lung damage in a mouse asthma model.
J. Exp. Med.
183:
195-201
34. Kumasaka, T., W. M. Quinlan, N. A. Doyle, T. P. Condon, J. Sligh, F. Takei, A. L. Beaudet, C. F. Bennett, and C. M. Doerschuk. 1996. Role of the intercellular adhesion molecule-1 (ICAM-1) in endotoxin-induced pneumonia evaluated using ICAM-1 antisense oligonucleotides, anti-ICAM-1 monoclonal antibodies, and ICAM-1 mutant mice. J. Clin. Invest. 97: 2362-2369 [Medline].
35.
Coyle, A. J.,
C. Erard,
S. Bertrand,
H. Pircher, and
G. Le Gros.
1995.
Virus-specific CD8+ cells can switch to interleukin 5 production and induce airway eosinophilia.
J. Exp. Med.
181:
1229-1233
36.
Hamelmann, E.,
A. Oshiba,
J. Paluh,
K. Bradley,
J. Loader,
T. A. Potter,
G. L. Larsen, and
E. W. Gelfand.
1996.
Requirement for CD8+ T cells in
the development of airway hyperresponsiveness in a murine model of airway sensitization.
J. Exp. Med.
183:
1719-1729
37.
Coyle, A. J.,
K. Wagner,
C. Bertrand,
S. Tsuyuki,
J. Bews, and
C. Heusser.
1996.
Central role of immunoglobulin (Ig) E in the induction of lung eosinophil infiltration and T helper 2 cell cytokine production: inhibition by a
non-anaphylactogenic anti-IgE antibody.
J. Exp. Med
183:
1303-1310
38.
Flores-Romo, L.,
J. Shields,
Y. Humbert,
P. Graber,
J. P. Aubry,
J. F. Gauchat,
G. Ayala,
B. Allet,
M. Chavez,
H. Bazin,
M. Capron, and
J. Bonnefoy.
1993.
Inhibition of an in vivo antigen-specific IgE response by antibodies to CD23.
Science
261:
1038-1041
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