N Krug, J Madden, AE Redington, P Lackie, R Djukanovic, U Schauer, ST Holgate, AJ Frew and PH Howarth
Immunopharmacology Group, Southampton, United Kingdom.

Atopic asthma is characterized by bronchial mucosal inflammation, involving eosinophils, mast cells, and lymphocytes. It has been suggested that the development and maintenance of this allergic inflammation is due to T-lymphocyte activation with predominant production of the cytokines interleukin 4 (IL-4) and IL-5. To address the ability of peripheral blood and bronchoalveolar lavage T-cells to generate IL-2, IL-4, or interferon gamma (IFN-gamma), we have employed a flow cytometric method which permits analysis of cytokine production at the single cell level within 5 h of obtaining cell samples. When stimulated with PMA and ionomycin, there was a greatly increased percentage of IFN-gamma-producing cells among bronchoalveolar lavage (BAL) T-cells from the subjects with asthma (median 74%), compared with atopic and nonatopic controls (35 and 43%, respectively; P>0.01). The proportion of BAL T-cells producing IL-4 was small (median 1.7%, range 0 to 7.8% in the asthmatic group). In all three groups, the proportion of BAL T-cells producing IL-2 or IFN-gamma was increased compared with T-cells from peripheral blood. There was no significant difference between the three groups in the percentage of BAL T-cells producing IL- 2, or in the percentage of peripheral blood T-cells producing IFN- gamma, IL-2 or IL-4. These findings indicate that IL-4 production is confined to a relatively small proportion of airway and blood T-cells and that there is selective enhancement of IFN-gamma production by airway T-cells in asthma.

This article has been cited by other articles:

				Y.-C. Su, M. S. Rolph, N. G. Hansbro, C. R. Mackay, and W. A. Sewell Granulocyte-Macrophage Colony-Stimulating Factor Is Required for Bronchial Eosinophilia in a Murine Model of Allergic Airway Inflammation J. Immunol., February 15, 2008; 180(4): 2600 - 2607. [Abstract] [Full Text] [PDF]

				J. C. Horvat, K. W. Beagley, M. A. Wade, J. A. Preston, N. G. Hansbro, D. K. Hickey, G. E. Kaiko, P. G. Gibson, P. S. Foster, and P. M. Hansbro Neonatal Chlamydial Infection Induces Mixed T-Cell Responses That Drive Allergic Airway Disease Am. J. Respir. Crit. Care Med., September 15, 2007; 176(6): 556 - 564. [Abstract] [Full Text] [PDF]

				S. Y. Thomas, A. Banerji, B. D. Medoff, C. M. Lilly, and A. D. Luster Multiple Chemokine Receptors, Including CCR6 and CXCR3, Regulate Antigen-Induced T Cell Homing to the Human Asthmatic Airway J. Immunol., August 1, 2007; 179(3): 1901 - 1912. [Abstract] [Full Text] [PDF]

				T. Kallinich, K. C. Beier, U. Wahn, P. Stock, and E. Hamelmann T-cell co-stimulatory molecules: their role in allergic immune reactions Eur. Respir. J., June 1, 2007; 29(6): 1246 - 1255. [Abstract] [Full Text] [PDF]

				S. N. Georas, J. Guo, U. De Fanis, and V. Casolaro T-helper cell type-2 regulation in allergic disease Eur. Respir. J., December 1, 2005; 26(6): 1119 - 1137. [Abstract] [Full Text] [PDF]

				A. J. M. van Oosterhout and N. Bloksma Regulatory T-lymphocytes in asthma Eur. Respir. J., November 1, 2005; 26(5): 918 - 932. [Abstract] [Full Text] [PDF]

				M. E. Stern, K. Siemasko, J. Gao, A. Duong, C. Beauregard, V. Calder, and J. Y. Niederkorn Role of Interferon-{gamma} in a Mouse Model of Allergic Conjunctivitis Invest. Ophthalmol. Vis. Sci., September 1, 2005; 46(9): 3239 - 3246. [Abstract] [Full Text] [PDF]

				M. J. Walter and M. J. Holtzman A Centennial History of Research on Asthma Pathogenesis Am. J. Respir. Cell Mol. Biol., June 1, 2005; 32(6): 483 - 489. [Full Text] [PDF]

				J. M. Matheson, V. J. Johnson, and M. I. Luster Immune Mediators in a Murine Model for Occupational Asthma: Studies with Toluene Diisocyanate Toxicol. Sci., March 1, 2005; 84(1): 99 - 109. [Abstract] [Full Text] [PDF]

				J. M. Matheson, V. J. Johnson, V. Vallyathan, and M. I. Luster Exposure and Immunological Determinants in a Murine Model for Toluene Diisocyanate (TDI) Asthma Toxicol. Sci., March 1, 2005; 84(1): 88 - 98. [Abstract] [Full Text] [PDF]

				S.-H. Cho, L. A. Stanciu, S. T. Holgate, and S. L. Johnston Increased Interleukin-4, Interleukin-5, and Interferon-{gamma} in Airway CD4+ and CD8+ T Cells in Atopic Asthma Am. J. Respir. Crit. Care Med., February 1, 2005; 171(3): 224 - 230. [Abstract] [Full Text] [PDF]

				R. K. Kumar, C. Herbert, D. C. Webb, L. Li, and P. S. Foster Effects of Anticytokine Therapy in a Mouse Model of Chronic Asthma Am. J. Respir. Crit. Care Med., November 15, 2004; 170(10): 1043 - 1048. [Abstract] [Full Text] [PDF]

				M. A. Aronica, S. McCarthy, S. Swaidani, D. Mitchell, M. Goral, J. R. Sheller, and M. Boothby Recall Helper T Cell Response: T Helper 1 Cell-resistant Allergic Susceptibility without Biasing Uncommitted CD4 T Cells Am. J. Respir. Crit. Care Med., March 1, 2004; 169(5): 587 - 595. [Abstract] [Full Text] [PDF]

				P. C. Fulkerson, N. Zimmermann, E. B. Brandt, E. E. Muntel, M. P. Doepker, J. L. Kavanaugh, A. Mishra, D. P. Witte, H. Zhang, J. M. Farber, et al. Negative regulation of eosinophil recruitment to the lung by the chemokine monokine induced by IFN-{gamma} (Mig, CXCL9) PNAS, February 17, 2004; 101(7): 1987 - 1992. [Abstract] [Full Text] [PDF]

				H. Hadeiba and R. M. Locksley Lung CD25 CD4 Regulatory T Cells Suppress Type 2 Immune Responses But Not Bronchial Hyperreactivity J. Immunol., June 1, 2003; 170(11): 5502 - 5510. [Abstract] [Full Text] [PDF]

				M. J. Abedin, Y. Kashio, M. Seki, K. Nakamura, and M. Hirashima Potential roles of galectins in myeloid differentiation into three different lineages J. Leukoc. Biol., May 1, 2003; 73(5): 650 - 656. [Abstract] [Full Text] [PDF]

				V Brown, T J Warke, M D Shields, and M Ennis T cell cytokine profiles in childhood asthma Thorax, April 1, 2003; 58(4): 311 - 316. [Abstract] [Full Text] [PDF]

				S. A. Hines, D. M. Stone, M. T. Hines, D. C. Alperin, D. P. Knowles, L. K. Norton, M. J. Hamilton, W. C. Davis, and T. C. McGuire Clearance of Virulent but Not Avirulent Rhodococcus equi from the Lungs of Adult Horses Is Associated with Intracytoplasmic Gamma Interferon Production by CD4+ and CD8+ T Lymphocytes Clin. Vaccine Immunol., March 1, 2003; 10(2): 208 - 215. [Abstract] [Full Text] [PDF]

				C. Schramm, U. Herz, J. Podlech, M. Protschka, S. Finotto, M. J. Reddehase, H. Kohler, P. R. Galle, A. W. Lohse, and M. Blessing TGF-{beta} Regulates Airway Responses Via T Cells J. Immunol., February 1, 2003; 170(3): 1313 - 1319. [Abstract] [Full Text] [PDF]

				A.-S. Charbonnier, H. Hammad, P. Gosset, G. A. Stewart, S. Alkan, A.-B. Tonnel, and J. Pestel Der p 1-pulsed myeloid and plasmacytoid dendritic cells from house dust mite-sensitized allergic patients dysregulate the T cell response J. Leukoc. Biol., January 1, 2003; 73(1): 91 - 99. [Abstract] [Full Text] [PDF]

				W. R. Henderson Jr., E. Y. Chi, J.-L. Teo, C. Nguyen, and M. Kahn A Small Molecule Inhibitor of Redox-Regulated NF-{kappa}B and Activator Protein-1 Transcription Blocks Allergic Airway Inflammation in a Mouse Asthma Model J. Immunol., November 1, 2002; 169(9): 5294 - 5299. [Abstract] [Full Text] [PDF]

				B. D. Medoff, A. Sauty, A. M. Tager, J. A. Maclean, R. N. Smith, A. Mathew, J. H. Dufour, and A. D. Luster IFN-{gamma}-Inducible Protein 10 (CXCL10) Contributes to Airway Hyperreactivity and Airway Inflammation in a Mouse Model of Asthma J. Immunol., May 15, 2002; 168(10): 5278 - 5286. [Abstract] [Full Text] [PDF]

				S. Chabot, Y. Kashio, M. Seki, Y. Shirato, K. Nakamura, N. Nishi, T. Nakamura, R. Matsumoto, and M. Hirashima Regulation of galectin-9 expression and release in Jurkat T cell line cells Glycobiology, February 1, 2002; 12(2): 111 - 118. [Abstract] [Full Text] [PDF]

				S. S. SALVI, K. SURESH BABU, and S. T. HOLGATE Is Asthma Really Due to a Polarized T Cell Response Toward a Helper T Cell Type 2 Phenotype? Am. J. Respir. Crit. Care Med., October 15, 2001; 164(8): 1343 - 1346. [Full Text] [PDF]

				C. A. Wu, L. Puddington, H. E. Whiteley, C. A. Yiamouyiannis, C. M. Schramm, F. Mohammadu, and R. S. Thrall Murine Cytomegalovirus Infection Alters Th1/Th2 Cytokine Expression, Decreases Airway Eosinophilia, and Enhances Mucus Production in Allergic Airway Disease J. Immunol., September 1, 2001; 167(5): 2798 - 2807. [Abstract] [Full Text] [PDF]

				A. Takaoka, Y. Tanaka, T. Tsuji, T. Jinushi, A. Hoshino, Y. Asakura, Y. Mita, K. Watanabe, S. Nakaike, Y. Togashi, et al. A Critical Role for Mouse CXC Chemokine(s) in Pulmonary Neutrophilia During Th Type 1-Dependent Airway Inflammation J. Immunol., August 15, 2001; 167(4): 2349 - 2353. [Abstract] [Full Text] [PDF]

				C. M. Fleming, H. He, A. Ciota, D. Perkins, and P. W. Finn Administration of Pentoxifylline During Allergen Sensitization Dissociates Pulmonary Allergic Inflammation from Airway Hyperresponsiveness J. Immunol., August 1, 2001; 167(3): 1703 - 1711. [Abstract] [Full Text] [PDF]

				J. G. Ford, D. Rennick, D. D. Donaldson, R. Venkayya, C. McArthur, E. Hansell, V. P. Kurup, M. Warnock, and G. Grunig IL-13 and IFN-{gamma}: Interactions in Lung Inflammation J. Immunol., August 1, 2001; 167(3): 1769 - 1777. [Abstract] [Full Text] [PDF]

				N. Krug, V. J. Erpenbeck, K. Balke, J. Petschallies, T. Tschernig, J. M. Hohlfeld, and H. Fabel Cytokine Profile of Bronchoalveolar Lavage-Derived CD4+, CD8+, and gamma delta T Cells in People with Asthma after Segmental Allergen Challenge Am. J. Respir. Cell Mol. Biol., July 1, 2001; 25(1): 125 - 131. [Abstract] [Full Text] [PDF]

				J. J. Campbell, C. E. Brightling, F. A. Symon, S. Qin, K. E. Murphy, M. Hodge, D. P. Andrew, L. Wu, E. C. Butcher, and A. J. Wardlaw Expression of Chemokine Receptors by Lung T Cells from Normal and Asthmatic Subjects J. Immunol., February 15, 2001; 166(4): 2842 - 2848. [Abstract] [Full Text] [PDF]

				J. WAHLSTRÖM, K. KATCHAR, H. WIGZELL, O. OLERUP, A. EKLUND, and J. GRUNEWALD Analysis of Intracellular Cytokines in CD4+ and CD8+ Lung and Blood T Cells in Sarcoidosis Am. J. Respir. Crit. Care Med., January 1, 2001; 163(1): 115 - 121. [Abstract] [Full Text]

				C. MARGUET, T. P. DEAN, and J. O. WARNER Soluble Intercellular Adhesion Molecule-1 (sICAM-1) and Interferon-Gamma in Bronchoalveolar Lavage Fluid from Children with Airway Diseases Am. J. Respir. Crit. Care Med., September 1, 2000; 162(3): 1016 - 1022. [Abstract] [Full Text]

				J. SCHWARZE, G. CIESLEWICZ, A. JOETHAM, T. IKEMURA, M. J. MAKELA, A. DAKHAMA, L. D. SHULTZ, M. C. LAMERS, and E. W. GELFAND Critical Roles for Interleukin-4 and Interleukin-5 during Respiratory Syncytial Virus Infection in the Development of Airway Hyperresponsiveness after Airway Sensitization Am. J. Respir. Crit. Care Med., August 1, 2000; 162(2): 380 - 386. [Abstract] [Full Text] [PDF]

				N. KRUG, W. W. CRUIKSHANK, T. TSCHERNIG, V. J. ERPENBECK, K. BALKE, J. M. HOHLFELD, D. M. CENTER, and H. FABEL Interleukin 16 and T-cell Chemoattractant Activity in Bronchoalveolar Lavage 24 Hours after Allergen Challenge in Asthma Am. J. Respir. Crit. Care Med., July 1, 2000; 162(1): 105 - 111. [Abstract] [Full Text]

				A. O. MAGNAN, L. G. MÉLY, C. A. CAMILLA, M. M. BADIER, F. A. MONTERO-JULIAN, C. M. GUILLOT, B. B. CASANO, S. J. PRATO, V. FERT, P. BONGRAND, et al. Assessment of the Th1/Th2 Paradigm in Whole Blood in Atopy and Asthma . Increased IFN-gamma -producing CD8+ T Cells in Asthma Am. J. Respir. Crit. Care Med., June 1, 2000; 161(6): 1790 - 1796. [Abstract] [Full Text]

				J. BOUSQUET, P. K. JEFFERY, W. W. BUSSE, M. JOHNSON, and A. M. VIGNOLA Asthma . From Bronchoconstriction to Airways Inflammation and Remodeling Am. J. Respir. Crit. Care Med., May 1, 2000; 161(5): 1720 - 1745. [Full Text]

				P. G. KNOTT, P. R. GATER, and C. P. BERTRAND Airway Inflammation Driven by Antigen-specific Resident Lung CD4+ T Cells in alpha beta -T Cell Receptor Transgenic Mice Am. J. Respir. Crit. Care Med., April 1, 2000; 161(4): 1340 - 1348. [Abstract] [Full Text]

				M. SCHUSTER, T. TSCHERNIG, N. KRUG, and R. PABST Lymphocytes Migrate from the Blood into the Bronchoalveolar Lavage and Lung Parenchyma in the Asthma Model of the Brown Norway Rat Am. J. Respir. Crit. Care Med., February 1, 2000; 161(2): 558 - 566. [Abstract] [Full Text]

				W. R. Henderson Jr., E. Y. Chi, and C. R. Maliszewski Soluble IL-4 Receptor Inhibits Airway Inflammation Following Allergen Challenge in a Mouse Model of Asthma J. Immunol., January 15, 2000; 164(2): 1086 - 1095. [Abstract] [Full Text] [PDF]

				C. E. Donovan, D. A. Mark, H. Z. He, H.-C. Liou, L. Kobzik, Y. Wang, G. T. De Sanctis, D. L. Perkins, and P. W. Finn NF-{kappa}B/Rel Transcription Factors: c-Rel Promotes Airway Hyperresponsiveness and Allergic Pulmonary Inflammation J. Immunol., December 15, 1999; 163(12): 6827 - 6833. [Abstract] [Full Text] [PDF]

				J. Schwarze, M. Makela, G. Cieslewicz, A. Dakhama, M. Lahn, T. Ikemura, A. Joetham, and E. W. Gelfand Transfer of the Enhancing Effect of Respiratory Syncytial Virus Infection on Subsequent Allergic Airway Sensitization by T Lymphocytes J. Immunol., November 15, 1999; 163(10): 5729 - 5734. [Abstract] [Full Text] [PDF]

				L. Cohn, R. J. Homer, N. Niu, and K. Bottomly T Helper 1 Cells and Interferon {gamma} Regulate Allergic Airway Inflammation and Mucus Production J. Exp. Med., November 1, 1999; 190(9): 1309 - 1318. [Abstract] [Full Text] [PDF]

				M. A. Aronica, A. L. Mora, D. B. Mitchell, P. W. Finn, J. E. Johnson, J. R. Sheller, and M. R. Boothby Preferential Role for NF-{kappa}B/Rel Signaling in the Type 1 But Not Type 2 T Cell-Dependent Immune Response In Vivo J. Immunol., November 1, 1999; 163(9): 5116 - 5124. [Abstract] [Full Text] [PDF]

				C. E Donovan and P. W Finn Immune mechanisms of childhood asthma Thorax, October 1, 1999; 54(10): 938 - 946. [Full Text]

				R. E. Déry and E. Y. Bissonnette IFN-gamma Potentiates the Release of TNF-alpha and MIP-1alpha by Alveolar Macrophages during Allergic Reactions Am. J. Respir. Cell Mol. Biol., March 1, 1999; 20(3): 407 - 412. [Abstract] [Full Text]

				J. Schwarze, G. Cieslewicz, E. Hamelmann, A. Joetham, L. D. Shultz, M. C. Lamers, and E. W. Gelfand IL-5 and Eosinophils Are Essential for the Development of Airway Hyperresponsiveness Following Acute Respiratory Syncytial Virus Infection J. Immunol., March 1, 1999; 162(5): 2997 - 3004. [Abstract] [Full Text] [PDF]

				D. A. Randolph, C. J. L. Carruthers, S. J. Szabo, K. M. Murphy, and D. D. Chaplin Modulation of Airway Inflammation by Passive Transfer of Allergen-Specific Th1 and Th2 Cells in a Mouse Model of Asthma J. Immunol., February 15, 1999; 162(4): 2375 - 2383. [Abstract] [Full Text] [PDF]

				M. Korsgren, C. G.A. Persson, F. Sundler, T. Bjerke, T. Hansson, B. J. Chambers, S. Hong, L. Van Kaer, H.-G. Ljunggren, and O. Korsgren Natural Killer Cells Determine Development of Allergen-induced Eosinophilic Airway Inflammation in Mice J. Exp. Med., February 1, 1999; 189(3): 553 - 562. [Abstract] [Full Text] [PDF]

				Z. Jaffar, K. Roberts, A. Pandit, P. Linsley, R. Djukanovic, and S. Holgate B7 Costimulation Is Required for IL-5 and IL-13 Secretion by Bronchial Biopsy Tissue of Atopic Asthmatic Subjects in Response to Allergen Stimulation Am. J. Respir. Cell Mol. Biol., January 1, 1999; 20(1): 153 - 162. [Abstract] [Full Text]

				L. Cohn, J. S. Tepper, and K. Bottomly Cutting Edge: IL-4-Independent Induction of Airway Hyperresponsiveness by Th2, But Not Th1, Cells J. Immunol., October 15, 1998; 161(8): 3813 - 3816. [Abstract] [Full Text] [PDF]

				U.-A. Temann, G. P. Geba, J. A. Rankin, and R. A. Flavell Expression of Interleukin 9 in the Lungs of  Transgenic Mice Causes Airway Inflammation, Mast Cell Hyperplasia, and Bronchial Hyperresponsiveness J. Exp. Med., October 5, 1998; 188(7): 1307 - 1320. [Abstract] [Full Text] [PDF]

				L. Li, Y. Xia, A. Nguyen, L. Feng, and D. Lo Th2-Induced Eotaxin Expression and Eosinophilia Coexist with Th1 Responses at the Effector Stage of Lung Inflammation J. Immunol., September 15, 1998; 161(6): 3128 - 3135. [Abstract] [Full Text] [PDF]

				N. KRUG, T. JUNG, U. NAPP, K. WAGNER, G. SCHULTZE-WERNINGHAUS, C. HEUSSER, C. H. L. RIEGER, U. SCHAUER, and H. FABEL Frequencies of T Cells Expressing Interleukin-4 and Interleukin-5 in Atopic Asthmatic Children . Comparison with Atopic Asthmatic Adults Am. J. Respir. Crit. Care Med., September 1, 1998; 158(3): 754 - 759. [Abstract] [Full Text] [PDF]

				S. J. TILL, S. R. DURHAM, K. RAJAKULASINGAM, M. HUMBERT, D. HUSTON, R. DICKASON, A. B. KAY, and C. J. CORRIGAN Allergen-induced Proliferation and Interleukin-5 Production by Bronchoalveolar Lavage and Blood T Cells after Segmental Allergen Challenge Am. J. Respir. Crit. Care Med., August 1, 1998; 158(2): 404 - 411. [Abstract] [Full Text] [PDF]

				M. Taguchi, D. Sampath, T. Koga, M. Castro, D. C. Look, S. Nakajima, and M. J. Holtzman Patterns for RANTES Secretion and Intercellular Adhesion Molecule 1 Expression Mediate Transepithelial T Cell Traffic Based on Analyses In Vitro and In Vivo J. Exp. Med., June 15, 1998; 187(12): 1927 - 1940. [Abstract] [Full Text] [PDF]

				R. J. Harbeck Clin. Vaccine Immunol., May 1, 1998; 5(3): 271 - 277. [Full Text]

				L. Cohn, R. J. Homer, A. Marinov, J. Rankin, and K. Bottomly Induction of Airway Mucus Production By T Helper 2 (Th2) Cells: A Critical Role For Interleukin 4 In Cell Recruitment But Not Mucus Production J. Exp. Med., November 17, 1997; 186(10): 1737 - 1747. [Abstract] [Full Text] [PDF]

				C. Leonard, V. Tormey, C. Burke, and L. W. Poulter Allergen-induced Cytokine Production in Atopic Disease and Its Relationship to Disease Severity Am. J. Respir. Cell Mol. Biol., September 1, 1997; 17(3): 368 - 375. [Abstract] [Full Text]

				J. J. Lee, M. P. McGarry, S. C. Farmer, K. L. Denzler, K. A. Larson, P. E. Carrigan, I. E. Brenneise, M. A. Horton, A. Haczku, E. W. Gelfand, et al. Interleukin-5 Expression in the Lung Epithelium of Transgenic Mice Leads to Pulmonary Changes Pathognomonic of Asthma J. Exp. Med., June 16, 1997; 185(12): 2143 - 2156. [Abstract] [Full Text] [PDF]