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Published ahead of print on April 17, 2003, doi:10.1165/rcmb.2003-0008OC
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American Journal of Respiratory Cell and Molecular Biology. Vol. 29, pp. 405-409, 2003
© 2003 American Thoracic Society
DOI: 10.1165/rcmb.2003-0008OC

Accelerated Airway Dendritic Cell Maturation, Trafficking, and Elimination in a Mouse Model of Asthma

Karim Vermaelen and Romain Pauwels

Department of Respiratory Diseases, Ghent University Hospital, Ghent, Belgium

Address correspondence to: Karim Vermaelen, Department of Respiratory Diseases, Ghent University Hospital 7K12ie, De Pintelaan 185, B-9000 Ghent, Belgium. E-mail Karim.Vermaelen{at}rug.ac.be


   Abstract
Top
 Abstract
Introduction
 Materials and Methods
 Results
 References
 
Pulmonary dendritic cells (DC) can induce both tolerogenic as well as inflammatory immune responses in the lung. Conversely, little is known about the impact of ongoing airway inflammation on pulmonary DC biology. In noninflammatory conditions, expression of T cell costimulatory molecules on mouse airway DCs is low and only upregulated after homing into draining thoracic lymph nodes. In this study, we reveal that ongoing allergic airway inflammation induces a premature upregulation of the T cell costimulatory molecules CD40, B7–2 and intercellular adhesion molecule 1 on DCs still present in the airways. In contrast, high surface expression of inducible costimulator ligand, involved in respiratory tolerance induction is restricted to DCs from noninflamed lungs. In addition, during inflammation the migratory flux of allergen-transporting airway DCs toward draining thoracic nodes increases both in amplitude as well as in speed. Remarkably, migratory DCs from inflamed airways are short-lived in the draining lymph nodes, a finding that is temporally associated with a marked loss of the antiapoptotic protein Bcl-2 in these cells. This study demonstrates the profound effects of ongoing allergen-driven airway inflammation on the dynamics of pulmonary DC physiology, a knowledge that could be exploited in the development of novel DC-based immunotherapies.

Abbreviations: airway-derived lymph node dendritic cells, AW-LNDCs • bronchoalveolar lavage, BAL • dendritic cells, DC • ethylenediamine tetraacetic acid, EDTA • fluorescein isothiocyanate, FITC • intercellular adhesion molecule 1, ICAM-1 • inducible costimulator ligand, ICOS-L • immunoglobulin, Ig • lymph node, LN • major histocompatibility complex, MHC • ovalbumin, OVA • phosphate-buffered saline, PBS • phycoerythrin, PE • thoracic lymph nodes, TLN • tumor necrosis factor, TNF


   Introduction
Top
 Abstract
 Introduction
Materials and Methods
 Results
 References
 
Allergic asthma, a disease of the airways with ever-increasing worldwide prevalence, is characterized by an inappropriate T helper 2 type immune response against non-pathogenic inhaled material. Airway dendritic cells (DCs) have come under scrutiny in the search for immunological flaws leading to the asthmatic phenotype. Recent studies suggest an essential role for airway DCs in deciding which pulmonary immune response ensues after contact with respiratory antigen. An emerging concept regards allergic immune responses as a deviation from the normal situation in which DCs capturing inert inhaled Ag induce tolerogenic, regulatory T cells within pulmonary lymph nodes (1). Under certain circumstances, DCs are capable of actively inducing (2) or maintaining allergic airway inflammation (3, 4). This knowledge is bringing the airway DC to the foreground as a novel cellular target in future anti-asthmatic therapies. However, any specific intervention at this level must come with a perfect understanding of this cell's physiology in the midst of a pathologic environment. In the steady state, pulmonary DCs are immature in terms of T cell costimulatory molecule expression and continuously sample antigens reaching the airway mucosa (5). Subsequently, these cells transport antigen to the T cell areas of draining thoracic lymph nodes (TLN) and become fully mature (6). This study reveals how experimental allergic airway inflammation profoundly influences some key features of pulmonary dendritic cell biology, i.e., maturation, migration, and terminal fate: the inflammatory milieu induces a strong local activation of DCs as these cells still reside in the airways, while simultaneously driving a massive number of short-lived allergen-transporting DCs into the thoracic lymph nodes.


   Materials and Methods
Top
 Abstract
 Introduction
 Materials and Methods
Results
 References
 
Animals and Immunizations
Mice were subjected to a well-documented allergen sensitization and exposure protocol which results in bronchoalveolar lavage (BAL) eosinophilia, BAL Th2 cytokine production, mononuclear and eosinophilic peribronchial infiltrates, mucus cell hyperplasia, elevated allergen-specific immunoglobulin (IgE), and airway hyperreactivity (7). Briefly, Male C57BL/6 mice, 6–8 wk old (purchased from Harlan, Zeist, The Netherlands) were immunized by intraperitoneal injection of 10 µg ovalbumin (OVA; Sigma, St. Louis, MO) complexed to 1 mg aluminum hydroxide (Al[OH]3). Two weeks later, the animals were exposed for 7 to 14 consecutive days to a daily 30 min of 1% ovalbumin (OVA) aerosol (OVA/OVA groups). Unless otherwise indicated, similar results were obtained in phosphate-buffered saline (PBS)/PBS, OVA/PBS, or PBS/OVA control groups, which is absence of allergic inflammation as verified on BAL cytocentrifuge preparations and absence of OVA-specific IgE in serum samples (not shown).

Intratracheal Instillation of Fluorescent Macromolecules
Fluorescein-conjugated ovalbumin (OVA-FITC; Molecular Probes Europe BV, Leiden, The Netherlands) was diluted in sterile PBS to a final concentration of 10 mg/ml. Intratracheal instillation was performed as previously described using disposable sterile and pyrogen-free polyurethane catheters (Insyte-W; Becton Dickinson, Madrid, Spain).

Preparation of Lung, BAL, and Lymph Node Single-Cell Suspensions
In trafficking experiments, thoracic lymph nodes were prelevated at different time points following OVA-FITC instillation, protected from light, and processed as outlined below. Alternatively, animals underwent BAL 24 h after the last aerosol exposure, using Hanks' balanced saline solution containing 0.5 mM ethylenediaminetetraacetic acid (EDTA). BAL samples were centrifuged, and the cell pellet was subjected to RBC lysis. Next, right heart catheterization and perfusion with saline–EDTA was performed to remove the pulmonary intravascular pool of cells. Lungs and lymph nodes were prelevated separately and were sequentially incubated in complete medium containing collagenase type 2 and DNase I, followed by 10 mM EDTA, RBC lysis, and finally passed through a cell strainer as detailed previously (6). Lung, BAL, and lymph node single cell suspensions were kept in FACS-EDTA buffer (PBS, 0.5% bovine serum albumin, 5 mM EDTA, 0.1% azide) until cell counting and immunofluorescent labeling.

Labeling of Single-Cell Suspensions for Flow Cytometry
Single-cell suspensions were pre-incubated with Fc-receptor blocking antibody (anti-CD16/CD32, clone 2.4G2) to reduce nonspecific binding. Monoclonal antibodies used to identify mouse DC populations were: biotinylated anti-CD11c (N418) followed by streptavidin–APC and PE-conjugated anti-IAb (AF6–120.1). In addition, the following panel of antibodies was used: phycoerythrin (PE)-conjugated anti-CD40 (3/23), anti-CD86 (GL-1), anti-CD54, anti–inducible costimulator ligand (ICOS-L)/B7RP-1 (HK5.3), and PE-conjugated isotype controls rat IgG2a and IgG2b. As a last step before analysis, cells were incubated with 7-amino-actinomycin (7AAD or Viaprobe) 10 min at room temperature for dead cell exclusion. Intracellular Bcl-2 protein levels were detected in fixed and permeabilized cells using PE-conjugated hamster anti-mouse Bcl-2 or hamster IgG staining control. All reagents were obtained from BD-Pharmingen (Erembodegem, Belgium) except clone N418 (kindly provided by M. Moser, ULB, Brussels, Belgium), PE anti-mouse CD54 (purchased from Research Diagnostics Inc., Flanders, NJ), and PE anti-mouse ICOS-L/B7RP-1, originally generated by Iwai and coworkers (8), (purchased from eBiosciences, San Diego, CA). Dendritic cells in lung tissues, airway lumen and thoracic lymph nodes were defined as detailed previously (6). Briefly, DCs within lung tissue (pulm-DCs) and BAL (BAL-DCs) were outlined as CD11c+/low autofluorescent cells. Within thoracic lymph nodes, a CD11cint-hi/MHCIIhi cluster was found to specifically contain DCs emigrating from the airway mucosa along with captured antigen (= "airway-derived lymph node DCs" or AW-LNDCs). In contrast, the CD11chi/MHCint LNDC cluster did not acquire and present antigen deposited in the airways ("non–airway-derived LNDCs" or NAW-LNDC) (6).


   Results
Top
 Abstract
 Introduction
 Materials and Methods
 Results
References
 
Allergic Airway Inflammation Induces In Situ Pulmonary DC Maturation
A first observation in this study is that ongoing allergen-driven airway inflammation leads to an upregulation of the T cell costimulatory molecules CD40, B7–2, and intercellular adhesion molecule (ICAM)-1 on DCs in the lung (Figure 1) . This upregulation was especially marked for pulmonary DCs within the airway lumen, sometimes approaching levels seen on terminally mature DCs in the draining TLN (e.g., B7-2). Although DCs are classically considered to mature upon homing into secondary lymphoid organs, only a few in vivo studies have described peripheral maturation of these cells during inflammation. In human atopic dermatitis, increased expression of a novel Th2-promoting inflammatory mediator (thymic stromal lymphopoietin) has been shown to be associated with phenotypic activation/maturation of skin dendritic cells in situ (9). In biopsies of giant cell arteritis, locally activated DCs are present with upregulated surface CCR7 and B7-2 (10). More relevantly, both B7-1 and B7-2 were found to be upregulated on pulmonary as well as thoracic lymph node DCs after allergen challenge in sensitized mice (11). In another report, a specific subset of long-lived DCs found in the BAL of allergic mice expressed high levels of B7-1 and CD40 (3). However, the modulations we observed were quantitatively different, which probably reflects differences in cell isolation procedures or the necessity to define relevant DC subgroups more precisely. Unexpectedly, ICOS-L behaved as an exception to the rule of costimulatory molecule upregulation following DC activation. A similar pattern was also observed in experiments in which human DCs were matured with tumor necrosis factor (TNF)-{alpha} in vitro (12). Murine ICOS-L (also known as B7RP-1, B7 h, or GL50) binds ICOS, which is induced on T cells upon activation (13). In vivo, ICOS–ICOS-L interaction has been described as an important signal for effector Th2 costimulation, optimal B-cell help (14) or even the interleukin-10–dependent induction of regulatory T cells in the lung (15). We now show that ongoing allergic airway inflammation induces a specific shift in airway DCs from a B7-low/ICOS-L–high to a B7-high/ICOS-L–low phenotype. In a similar model of experimental allergic asthma, blockade of ICOS during the effector phase of the immune response attenuated allergic airway inflammation, although less profoundly than B7-inhibition using CTLA-4-Ig (16). In contrast, blockade of ICOS-L during exposure of naive animals to inhaled antigen annihilated a default pathway of respiratory tolerance induction (15). These contrasting outcomes are probably due to differences in sensitization, antigen delivery (i.e., intranasal versus inhaled aerosol) and the presence of ongoing airway inflammation. Future studies will determine whether the net response after respiratory antigen encounter depends on the ratio between DC B7- and ICOS-L–contributed signals and the presence or absence of inflammation in the airways.



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  		Figure 1. Expression of surface molecules involved in antigen presentation and T cell costimulation on DCs from different pulmonary compartments, i.e., lung tissue (pulm-DCs), airway lumen (BAL-DCs), and DCs in thoracic lymph nodes (LNDCs). In the TLN, MHC class II positivity was determined within all CD11c+ cells, whereas T cell costimulatory molecule expression was examined within the airway-derived LNDC subpopulation (AW-LNDCs) which is MHCII-high/CD11c-med-high. There was no difference between costimulatory molecule expression when examined within the AW-LNDC cluster as a whole compared with OVA-FITC+ CD11c+ LNDCs only. Gray histograms indicate specific marker, white semitransparent histograms indicate isotype control staining. The numbers indicate mean fluorescence intensity relative to isotype control, calculated from 4–6 mice per treatment group.

 
Allergic Airway Inflammation Amplifies the Speed and Magnitude of Airway DC Trafficking
Allergic airway inflammation induced a marked increase in absolute DC numbers in the lung interstitium as well as the airway lumen, with the relative increase especially pronounced in the latter compartment (Figures 2A and 2B) . Within the thoracic lymph node (TLN), CD11c+ lymph node (LN) cells were augmented as well (Figure 2C). The elevated number of TLN DCs was primarily due to an expansion of the airway-derived lymph node DC cluster (Figure 3) . A massively increased and accelerated influx of allergen-transporting DCs from the airways appeared at the basis of this phenomenon (Figure 4) . This was demonstrated by relying on the capacity of airway DCs to endocytose and transport the soluble fluorescent macromolecule OVA-FITC deposited on the airway mucosa (6). In noninflammatory conditions (PBS/PBS groups), a peak number of FITC+ AW-LNDCs was reached 24–48 h after intratracheal OVA-FITC instillation, and all FITC+ DCs had disappeared from the TLN by Day 7 after antigen uptake. Allergic airway inflammation (OVA/OVA groups) had a profound impact on these baseline kinetics: the peak accumulation of DCs was reached much earlier (8 h after allergen uptake in the airways), whereas the amplitude of this peak influx was increased ~ 5-fold compared with nonallergic mice. Although allergic airway inflammation could induce leakiness of the epithelial barrier through damage of the respiratory epithelium, passive transfer of OVA-FITC to the TLN still remained a marginal phenomenon. Indeed, uptake by non–AW-LNDCs during full-blown inflammation represented at most 10% of the number of FITC+ migratory AW-LNDC (not shown), while we have previously shown that both LNDC subsets can equally endocytose OVA-FITC when exposed to the same dose in vitro (6). Our findings corroborate a recent report in which the allergic airway environment was found to stimulate the migration of in vitro-cultured, adoptively transferred DCs toward draining thoracic LN (17). The increased emigration toward thoracic LN is not surprising given that DC maturation not only involves increased T cell costimulatory molecule expression, but also a distinct switch in chemokine responsiveness favoring the homing of DCs toward secondary lymphoid organs (18). Further investigations will be necessary to identify the inflammatory mediators underlying this phenomenon. A plausible candidate could be increased local production of TNF-{alpha}. TNF-{alpha} protein levels are known to be upregulated in the airways of asthmatics (19). In the skin, TNF-{alpha} can both stimulate epidermal dendritic cell emigration as well as recruitment (20), which is in line with our in vivo observations in the lung. Moreover, earlier studies have described an increased trafficking of lung and gut mucosal dendritic cells after LPS stimulation (21, 22), an effect which is known to be largely TNF-{alpha}–dependent.



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  		Figure 2. Following a 7-d aerosol exposure period, DCs were enumerated by flow cytometry in (A) lung tissue, (B) airway lumen (CD11c+/low-autofluorescent cells), and (C) draining TLN (CD11c+ cells). Light bars indicate control groups (only PBS/PBS mice are shown; similar results were found in other noninflammatory groups, i.e., OVA/PBS and PBS/OVA), dark bars depict OVA-sensitized and -exposed animals (n = 6 mice per group). Differences were statistically significant (Student's t test, P < 0.05).

 


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  		Figure 3. Thoracic lymph nodes were stained with a combination of anti-CD11c and anti-MHCII to delineate airway-derived and non–airway-derived lymph node DCs. (A) Allergic airway inflammation induces a selective expansion of the AW-LNDCs cluster as seen on the density plot. (B) AW-LNDC increase expressed in absolute numbers.

 


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  		Figure 4. Mice sensitized to PBS or OVA in adjuvant and later exposed to PBS or OVA aerosol underwent intratracheal instillation of FITC-ovalbumin at Day 7 of the aerosol exposure period. FITC+ airway-derived DCs were enumerated in the draining thoracic lymph nodes at different time intervals thereafter. The aerosol exposure was maintained for the whole duration of the kinetics study. Results for the noninflammatory PBS/OVA group were similar to the PBS/PBS group and were omitted for clarity (n = 6–7 mice per time point). One representative experiment out of three is shown. Filled circles, OVA/OVA; open circles with solid line, OVA/PBS; open circles with dotted line, PBS/PBS.

 
Allergic Airway Inflammation Accelerates the Clearance of Migratory DCs from the TLN
Interestingly, the initial inflammatory rush of allergen-transporting DCs is quickly followed by an accelerated disappearance of these cells from the draining lymph nodes (Figure 4): between Day 1 and 2 after instillation of OVA-FITC, ~ 93% of the allergen-transporting DCs were cleared from the LN of OVA/OVA mice compared with less than 50% in PBS/PBS mice. By Day 3, virtually all the allergen-transporting DCs had disappeared from the TLN of OVA/OVA animals. This is very similar to observations made by Ingulli and colleagues using an adoptive transfer model: analysis of DC–T cell encounters within peripheral LN revealed a premature clearance of DCs only in the context of Ag-specific DC-T cell interaction (23). Because migratory DCs in the LN do not progress toward efferent lymphatic vessels (24), their number at any given time point is a balance between cellular influx and the rate of cell death. An emerging concept regarding the terminal fate of DCs within LN confronts death signals induced by antigen-specific MHC class II engagement against survival-promoting signals originating from CD40–CD40L interactions (25, 26). We speculate that a similar mechanism might come into play in our in vivo model. Indeed, CD40 ligation has been shown to rescue DCs from apoptosis with concomitant upregulation of intracellular Bcl-2 (27). The importance of Bcl-2 in prolonging DC survival in vivo has been recently illustrated using transgenic animals in which Bcl-2 was specifically overexpressed in DCs (28): functionally, this resulted in an enhanced T-helper cell–mediated immune response. Furthermore, induction of full DC maturation (the last step before apoptosis) is associated with rapid downregulation of intracellular Bcl-2 (29). Our observations reveal that during full-blown allergic airway inflammation, freshly immigrating allergen-loaded DCs in the TLN have upregulated levels of Bcl-2 compared with migratory DCs from noninflammatory controls (Figure 5) . However, further stay in the TLN induces a rapid and massive elimination of these cells that correlates with a marked loss of intracellular Bcl-2.



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  		Figure 5. Flow cytometric evaluation of intracellular Bcl-2 protein levels within allergen-transporting airway-derived DCs in thoracic lymph nodes. OVA-FITC was given intratracheally 24 h after the last aerosol exposure, and TLN were prelevated 24 and 48 h later (corresponding to the timeframe of peak accumulation and subsequent clearance of allergen-transporting AW-LNDCs, respectively). Bcl-2 levels within FITC+/CD11c+ cells were expressed relative to background as determined by isotype control staining. n = 7–8 mice per group. Open circles, PBS/PBS; filled circles, OVA/OVA.

 
It has often been suggested that the elimination of DCs within LN acts to prevent unrestrained immune stimulation. However, such kinetics should be integrated over the whole time period of antigen exposure: indeed, in our experiments the net result of ongoing inflammation is a continuous massive presence of fully mature allergen-transporting DCs in the LN, however short-lived these cells may be. Interestingly, the allergen-exposure regimen used here results in respiratory tolerance induction when prolonged beyond 2–3 wk. It is known that excessive stimulation by high DC densities can induce T cell deletion (30). Therefore, it is tempting to speculate that the increased throughput of allergen-transporting DCs might initiate the development of tolerance in this model by progressively inactivating the pool of antigen-specific central memory T cells within mucosal lymph nodes.

In summary, our study sketches a complex picture of pulmonary DC biology in the midst of allergic airway inflammation. In the airways, we speculate that the local DC maturation, along with the immediate contact with aeroallergen and the recruitment of effector T and B cells, provide an adequate environment for an in situ maintenance of the chronic airway inflammation. At the same time, the massive influx into mucosal lymph nodes of short-lived, allergen-capturing airway DCs is a finding whose physiologic significance will have to be explored in future studies.


   Acknowledgments
 
The authors thank G. Barbier, E. Castrique, C. Snauwaert, M. Mouton, K. De Saedeleer, A. Neessen, and I. De Borle for their technical assistance. This work was supported by the Fund for Scientific Research in Flanders (FWO Vlaanderen, Research Project G.0393.99), and by the Concerted Research Initiative of the University of Ghent (GOA Project 98-6). K.V. is a doctoral research fellow of the Fund for Scientific Research in Flanders (FWO Vlaanderen).

Received in original form January 9, 2003

Received in final form March 11, 2003


   References
Top
 Abstract
 Introduction
 Materials and Methods
 Results
 References
 

  1. Akbari, O., R. H. DeKruyff, and D. T. Umetsu. 2001. Pulmonary dendritic cells producing IL-10 mediate tolerance induced by respiratory exposure to antigen. Nat. Immunol. 2:725–731.[CrossRef][Medline]
  2. Lambrecht, B. N., M. De Veerman, A. J. Coyle, J. C. Gutierrez-Ramos, K. Thielemans, and R. A. Pauwels. 2000. Myeloid dendritic cells induce Th2 responses to inhaled antigen, leading to eosinophilic airway inflammation. J. Clin. Invest. 106:551–559.[Medline]
  3. Julia, V., E. M. Hessel, L. Malherbe, N. Glaichenhaus, A. O'Garra, and R. L. Coffman. 2002. A restricted subset of dendritic cells captures airborne antigens and remains able to activate specific T cells long after antigen exposure. Immunity 16:271–283.[CrossRef][Medline]
  4. Lambrecht, B. N., B. Salomon, D. Klatzmann, and R. A. Pauwels. 1998. Dendritic cells are required for the development of chronic eosinophilic airway inflammation in response to inhaled antigen in sensitized mice. J. Immunol. 160:4090–4097.[Abstract/Free Full Text]
  5. Cochand, L., P. Isler, F. Songeon, and L. P. Nicod. 1999. Human lung dendritic cells have an immature phenotype with efficient mannose receptors. Am. J. Respir. Cell Mol. Biol. 21:547–554.[Abstract/Free Full Text]
  6. Vermaelen, K. Y., I. Carro-Muino, B. N. Lambrecht, and R. A. Pauwels. 2001. Specific migratory dendritic cells rapidly transport antigen from the airways to the thoracic lymph nodes. J. Exp. Med. 193:51–60.
  7. Brusselle, G., J. Kips, G. Joos, H. Bluethmann, and R. Pauwels. 1995. Allergen-induced airway inflammation and bronchial responsiveness in wild-type and interleukin-4–deficient mice. Am. J. Respir. Cell Mol. Biol. 12:254–259.[Abstract]
  8. Iwai, H., Y. Kozono, S. Hirose, H. Akiba, H. Yagita, K. Okumura, H. Kohsaka, N. Miyasaka, and M. Azuma. 2002. Amelioration of collagen-induced arthritis by blockade of inducible costimulator-b7 homologous protein costimulation. J. Immunol. 169:4332–4339.[Abstract/Free Full Text]
  9. Soumelis, V., P. A. Reche, H. Kanzler, W. Yuan, G. Edward, B. Homey, M. Gilliet, S. Ho, S. Antonenko, A. Lauerma, K. Smith, D. Gorman, S. Zurawski, J. Abrams, S. Menon, T. McClanahan, R. de Waal-Malefyt Rd, F. Bazan, R. A. Kastelein, and Y. J. Liu. 2002. Human epithelial cells trigger dendritic cell mediated allergic inflammation by producing TSLP. Nat. Immunol. 3:673–680.[Medline]
  10. Krupa, W. M., M. Dewan, M. S. Jeon, P. J. Kurtin, B. R. Younge, J. J. Goronzy, and C. M. Weyand. 2002. Trapping of misdirected dendritic cells in the granulomatous lesions of giant cell arteritis. Am. J. Pathol. 161:1815–1823.[Abstract/Free Full Text]
  11. Gajewska, B. U., F. K. Swirski, D. Alvarez, S. A. Ritz, S. Goncharova, M. Cundall, D. P. Snider, A. J. Coyle, J. C. Gutierrez-Ramos, M. R. Stampfli, and M. Jordana. 2001. Temporal-spatial analysis of the immune response in a murine model of ovalbumin-induced airways inflammation. Am. J. Respir. Cell Mol. Biol. 25:326–334.[Abstract/Free Full Text]
  12. Yoshinaga, S. K., M. Zhang, J. Pistillo, T. Horan, S. D. Khare, K. Miner, M. Sonnenberg, T. Boone, D. Brankow, T. Dai, J. Delaney, H. Han, A. Hui, T. Kohno, R. Manoukian, J. S. Whoriskey, and M. A. Coccia. 2000. Characterization of a new human B7-related protein: B7RP-1 is the ligand to the co-stimulatory protein ICOS. Int. Immunol. 12:1439–1447.[Abstract/Free Full Text]
  13. Yoshinaga, S. K., J. S. Whoriskey, S. D. Khare, U. Sarmiento, J. Guo, T. Horan, G. Shih, M. Zhang, M. A. Coccia, T. Kohno, A. Tafuri-Bladt, D. Brankow, P. Campbell, D. Chang, L. Chiu, T. Dai, G. Duncan, G. S. Elliott, A. Hui, S. M. McCabe, S. Scully, A. Shahinian, C. L. Shaklee, G. Van, T. W. Mak, and G. Senaldi. 1999. T-cell co-stimulation through B7RP-1 and ICOS. Nature 402:827–832.[CrossRef][Medline]
  14. Coyle, A. J., S. Lehar, C. Lloyd, J. Tian, T. Delaney, S. Manning, T. Nguyen, T. Burwell, H. Schneider, J. A. Gonzalo, M. Gosselin, L. R. Owen, C. E. Rudd, and J. C. Gutierrez-Ramos. 2000. The CD28-related molecule ICOS is required for effective T cell-dependent immune responses. Immunity 13:95–105.[CrossRef][Medline]
  15. Akbari, O., G. J. Freeman, E. H. Meyer, E. A. Greenfield, T. T. Chang, A. H. Sharpe, G. Berry, R. H. DeKruyff, and D. T. Umetsu. 2002. Antigen-specific regulatory T cells develop via the ICOS-ICOS-ligand pathway and inhibit allergen-induced airway hyperreactivity. Nat. Med. 8:1024–1032.[CrossRef][Medline]
  16. Gonzalo, J. A., J. Tian, T. Delaney, J. Corcoran, J. B. Rottman, J. Lora, A. Al-garawi, R. Kroczek, J. C. Gutierrez-Ramos, and A. J. Coyle. 2001. ICOS is critical for T helper cell-mediated lung mucosal inflammatory responses. Nat Immunol 2:597–604.[CrossRef][Medline]
  17. Van Rijt, L. S., J. B. Prins, P. J. Leenen, K. Thielemans, V. C. De Vries, H. C. Hoogsteden, and B. N. Lambrecht. 2002. Allergen-induced accumulation of airway dendritic cells is supported by an increase in CD31hiLy-6Cneg bone marrow precursors in a mouse model of asthma. Blood 100:3663–3671.[Abstract/Free Full Text]
  18. Kellermann, S. A., S. Hudak, E. R. Oldham, Y. J. Liu, and L. M. McEvoy. 1999. The CC chemokine receptor-7 ligands 6Ckine and macrophage inflammatory protein-3 beta are potent chemoattractants for in vitro- and in vivo- derived dendritic cells. J. Immunol. 162:3859–3864.[Abstract/Free Full Text]
  19. Keatings, V. M., P. D. Collins, D. M. Scott, and P. J. Barnes. 1996. Differences in interleukin-8 and tumor necrosis factor-{alpha} in induced sputum from patients with chronic obstructive pulmonary disease or asthma. Am. J. Respir. Crit. Care Med. 153:530–534.[Abstract]
  20. Cumberbatch, M., R. J. Dearman, and I. Kimber. 1999. Induction by tumour necrosis factor alpha of dose-related changes in Langerhans cell frequency in mice. Arch. Dermatol. Res. 291:453–458.[CrossRef][Medline]
  21. Schon-Hegrad, M. A., J. Oliver, P. G. McMenamin, and P. G. Holt. 1991. Studies on the density, distribution, and surface phenotype of intraepithelial class II major histocompatibility complex antigen (Ia)- bearing dendritic cells (DC) in the conducting airways. J. Exp. Med. 173:1345–1356.[Abstract/Free Full Text]
  22. MacPherson, G. G., C. D. Jenkins, M. J. Stein, and C. Edwards. 1995. Endotoxin-mediated dendritic cell release from the intestine: characterization of released dendritic cells and TNF dependence. J. Immunol. 154:1317–1322.[Abstract]
  23. Ingulli, E., A. Mondino, A. Khoruts, and M. K. Jenkins. 1997. In vivo detection of dendritic cell antigen presentation to CD4(+) T cells. J. Exp. Med. 185:2133–2141.[Abstract/Free Full Text]
  24. Pugh, C. W., G. G. MacPherson, and H. W. Steer. 1983. Characterization of nonlymphoid cells derived from rat peripheral lymph. J. Exp. Med. 157:1758–1779.[Abstract/Free Full Text]
  25. McLellan, A., M. Heldmann, G. Terbeck, F. Weih, C. Linden, E. B. Brocker, M. Leverkus, and E. Kampgen. 2000. MHC class II and CD40 play opposing roles in dendritic cell survival. Eur. J. Immunol. 30:2612–2619.[CrossRef][Medline]
  26. Matsue, H., D. Edelbaum, A. C. Hartmann, A. Morita, P. R. Bergstresser, H. Yagita, K. Okumura, and A. Takashima. 1999. Dendritic cells undergo rapid apoptosis in vitro during antigen-specific interaction with CD4+ T cells. J. Immunol. 162:5287–5298.[Abstract/Free Full Text]
  27. Bjorck, P., J. Banchereau, and L. Flores-Romo. 1997. CD40 ligation counteracts Fas-induced apoptosis of human dendritic cells. Int. Immunol. 9:365–372.[Abstract/Free Full Text]
  28. Nopora, A., and T. Brocker. 2002. Bcl-2 controls dendritic cell longevity in vivo. J. Immunol. 169:3006–3014.[Abstract/Free Full Text]
  29. Granucci, F., C. Vizzardelli, N. Pavelka, S. Feau, M. Persico, E. Virzi, M. Rescigno, G. Moro, and P. Ricciardi-Castagnoli. 2001. Inducible IL-2 production by dendritic cells revealed by global gene expression analysis. Nat. Immunol. 2:882–888.[CrossRef][Medline]
  30. Langenkamp, A., G. Casorati, C. Garavaglia, P. Dellabona, A. Lanzavecchia, and F. Sallusto. 2002. T cell priming by dendritic cells: thresholds for proliferation, differentiation and death and intraclonal functional diversification. Eur. J. Immunol. 32:2046–2054.[CrossRef][Medline]



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