The Journal of Immunology, Vol 147, Issue 9 2942-2949, Copyright © 1991 by American Association of Immunologists

ARTICLES

Human atopen-specific types 1 and 2 T helper cell clones

EA Wierenga, M Snoek, HM Jansen, JD Bos, RA van Lier and ML Kapsenberg
Department of Cell Biology and Histology, University of Amsterdam, The Netherlands.

Eight representative T lymphocyte clones (TLC) randomly selected from previously described panels of CD4+ housedust mite Dermatophagoides pteronyssinus (Dp)-specific TLC from atopic and nonatopic donors were studied in more detail in a comparative investigation. The TLC from the atopic donors closely resembled murine type 2 Th (Th2) cells by secreting substantial IL-4, IL-5, IL-6, TNF-alpha, and granulocyte- macrophage (GM)-CSF, minimal IFN-gamma, and relatively little IL-2. In contrast, the nonatopic's TLC resembled murine type 1 Th (TH1) cells by secreting substantial IFN-gamma, IL-2, TNF-alpha, and GM-CSF, no IL-4, and little IL-5. A difference with murine Th1 cells was their additional secretion of IL-6. These cytokine profiles were consistent upon stimulation via different activation pathways including stimulation with specific Dp Ag, mitogenic lectins, and antibodies to CD2, CD3, or CD28. The observed differences in IL-2 secretion, however, were most evident upon stimulation with anti-CD28. If TLC cells were cultured with highly purified B cells and stimulated with anti-CD3 in the absence of exogenous IL-4, IgE synthesis was induced only in cultures with the atopics' Th2 clones, which could be completely abrogated by anti-IL-4. The mere presence of exogenous rIL-4, however, did not result in IgE synthesis, nor did unstimulated TLC cells alone. But if unstimulated TLC cells (that proved not to secrete detectable amounts of cytokines) were added together with rIL-4, again IgE synthesis was induced only in cultures with the atopics' Th2 clones, suggesting the involvement of an additional, as yet unidentified accessory helper function of the atopics' Th2 clones for IgE induction. Unstimulated Th2 clones showed a significantly higher expression of CD28 than the Th1 clones, but three days after stimulation, CD28 expression was elevated to comparable levels on both subsets. When added to B cells at this time point, together with rIL-4 and anti-IFN- gamma, still only the atopics' Th2 clones supported IgE synthesis, arguing against a role for CD28 in this accessory helper function. Whereas the atopics' Th2 clones were excellent helper cells for IgE induction, a unique property of the nonatopic's Th1 clones was their cytolytic activity toward autologous APC which could be induced by specific Dp Ag and by anti-CD3. The present data provide clear evidence for the existence of Th1 and Th2 cells in man.

This article has been cited by other articles:

				M. A. Kolber Impact of Immune Plasticity on Development of Cellular Memory Responses to Human Immunodeficiency Virus Type 1 Clin. Vaccine Immunol., November 1, 2004; 11(6): 1002 - 1007. [Full Text] [PDF]

				E. M. M. van Leeuwen, E. B. M. Remmerswaal, M. T. M. Vossen, A. T. Rowshani, P. M. E. Wertheim-van Dillen, R. A. W. van Lier, and I. J. M. ten Berge Emergence of a CD4+CD28- Granzyme B+, Cytomegalovirus-Specific T Cell Subset after Recovery of Primary Cytomegalovirus Infection J. Immunol., August 1, 2004; 173(3): 1834 - 1841. [Abstract] [Full Text] [PDF]

				G. T. F. Schwenger, C. C. Kok, E. Arthaningtyas, M. A. Thomas, C. J. Sanderson, and V. A. Mordvinov Specific Activation of Human Interleukin-5 Depends on de Novo Synthesis of an AP-1 Complex J. Biol. Chem., November 27, 2002; 277(49): 47022 - 47027. [Abstract] [Full Text] [PDF]

				E. J. Feron, V. N. A. Klaren, E. A. Wierenga, G. M. G. M. Verjans, and A. Kijlstra Characterization of Toxoplasma gondii-Specific T Cells Recovered from Vitreous Fluid of Patients with Ocular Toxoplasmosis Invest. Ophthalmol. Vis. Sci., December 1, 2001; 42(13): 3228 - 3232. [Abstract] [Full Text] [PDF]

				J. A. Woodfolk and T. A. E. Platts-Mills Diversity of the Human Allergen-Specific T Cell Repertoire Associated with Distinct Skin Test Reactions: Delayed-Type Hypersensitivity-Associated Major Epitopes Induce Th1- and Th2-Dominated Responses J. Immunol., November 1, 2001; 167(9): 5412 - 5419. [Abstract] [Full Text] [PDF]

				K. G. Tournoy, J. C. Kips, and R. A. Pauwels The Allergen-Induced Airway Hyperresponsiveness in a Human-Mouse Chimera Model of Asthma Is T Cell and IL-4 and IL-5 Dependent J. Immunol., June 1, 2001; 166(11): 6982 - 6991. [Abstract] [Full Text] [PDF]

				D. M. Walter, C. P. Wong, R. H. DeKruyff, G. J. Berry, S. Levy, and D. T. Umetsu IL-18 Gene Transfer by Adenovirus Prevents the Development of and Reverses Established Allergen-Induced Airway Hyperreactivity J. Immunol., May 15, 2001; 166(10): 6392 - 6398. [Abstract] [Full Text] [PDF]

				S. D. Hurst, B. W. P. Seymour, T. Muchamuel, V. P. Kurup, and R. L. Coffman Modulation of Inhaled Antigen-Induced IgE Tolerance by Ongoing Th2 Responses in the Lung J. Immunol., April 15, 2001; 166(8): 4922 - 4930. [Abstract] [Full Text] [PDF]

				M. Bracke, E. van de Graaf, J.-W. J Lammers, P. J Coffer, and L. Koenderman In vivo priming of Fc{alpha}R functioning on eosinophils of allergic asthmatics J. Leukoc. Biol., November 1, 2000; 68(5): 655 - 661. [Abstract] [Full Text]

				J. A. Woodfolk, S.-S. J. Sung, D. C. Benjamin, J. K. Lee, and T. A. E. Platts-Mills Distinct Human T Cell Repertoires Mediate Immediate and Delayed-Type Hypersensitivity to the Trichophyton Antigen, Tri r 2 J. Immunol., October 15, 2000; 165(8): 4379 - 4387. [Abstract] [Full Text] [PDF]

				E. M. Varga, P. Wachholz, K. T. Nouri-Aria, A. Verhoef, C. J. Corrigan, S. J. Till, and S. R. Durham T Cells from Human Allergen-Induced Late Asthmatic Responses Express IL-12 Receptor {beta}2 Subunit mRNA and Respond to IL-12 In Vitro J. Immunol., September 1, 2000; 165(5): 2877 - 2885. [Abstract] [Full Text] [PDF]

				V. Rodrigues Jr., K. Piper, P. Couissinier-Paris, O. Bacelar, H. Dessein, and A. J. Dessein Genetic Control of Schistosome Infections by the SM1 Locus of the 5q31-q33 Region Is Linked to Differentiation of Type 2 Helper T Lymphocytes Infect. Immun., September 1, 1999; 67(9): 4689 - 4692. [Abstract] [Full Text] [PDF]

				J. A. Woodfolk, L. M. Wheatley, R. V. Piyasena, D. C. Benjamin, and T. A. E. Platts-Mills Trichophyton Antigens Associated with IgE Antibodies and Delayed Type Hypersensitivity. SEQUENCE HOMOLOGY TO TWO FAMILIES OF SERINE PROTEINASES J. Biol. Chem., November 6, 1998; 273(45): 29489 - 29496. [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]

				C. E. Verhagen, T. C. T. M. van der Pouw Kraan, A. A. M. Buffing, M. A. Chand, W. R. Faber, L. A. Aarden, and P. K. Das Type 1- and Type 2-Like Lesional Skin-Derived Mycobacterium leprae-Responsive T Cell Clones Are Characterized by Coexpression of IFN-{gamma}/TNF-{alpha} and IL-4/IL-5/IL-13, Respectively J. Immunol., March 1, 1998; 160(5): 2380 - 2387. [Abstract] [Full Text] [PDF]

				G. G. Bashian, C. M. Braun, S.-K. Huang, A. Kagey-Sobotka, L. M. Lichtenstein, and D. M. Essayan Differential Regulation of Human, Antigen-specific Th1 and Th2 Responses by the B-7 Homologues, CD80 and CD86 Am. J. Respir. Cell Mol. Biol., August 1, 1997; 17(2): 235 - 242. [Abstract] [Full Text]

				D. M. Essayan, A. Kagey-Sobotka, L. M. Lichtenstein, and S.-K. Huang Differential Regulation of Human Antigen-Specific Th1 and Th2 Lymphocyte Responses by Isozyme Selective Cyclic Nucleotide Phosphodiesterase Inhibitors J. Pharmacol. Exp. Ther., July 1, 1997; 282(1): 505 - 512. [Abstract] [Full Text]