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J. Exp. Med.
© The Rockefeller University Press
0022-1007/96/12/2129/12 $2.00
Volume 184 December 1996 2129-2140

gamma delta T Cells from Tolerized alpha beta T Cell Receptor (TCR)-deficient Mice Inhibit Contact Sensitivity-Effector T Cells In Vivo, and Their Interferon-gamma Production In Vitro

By Marian Szczepanik,* Laurel R. Anderson,Dagger § Hiroko Ushio,Dagger Wlodzimierz Ptak,* Michael J. Owen,par Adrian C. Hayday,§ and Philip W. AskenaseDagger

From the * Department of Immunology, College of Medicine, Jagiellonian University, Krakow, Poland; Dagger  Section of Allergy and Clinical Immunology, Dept. of Internal Medicine, Yale University School of Medicine, New Haven, Connecticut 06520-8013; § Department of Biology and Section of Immunobiology, Kline Biology Tower, Yale University, New Haven, Connecticut 06520; and par  Imperial Cancer Research Foundation, London, England WZCA 3PX

Contact sensitivity (CS) responses to reactive hapten Ag, such as picryl chloride (PCl) or oxazolone (OX), are classical examples of T cell-mediated immune responses in vivo that are clearly subject to multifaceted regulation. There is abundant evidence that downregulation of CS may be mediated by T cells exposed to high doses of Ag. This is termed high dose Ag tolerance. To clarify the T cell types that effect CS responses and mediate their downregulation, we have undertaken studies of CS in mice congenitally deficient in specific subsets of lymphocytes. The first such studies, using alpha beta T cell-deficient (TCRalpha -/-) mice, are presented here. The results clearly show that TCRalpha -/- mice cannot mount CS, implicating alpha beta T cells as the critical CS-effector cells. However, TCRalpha -/- mice can, after high dose tolerance, downregulate alpha +/+ CS-effector T cells adoptively transferred into them. By mixing ex vivo and then adoptive cell transfers in vivo, the active downregulatory cells in tolerized alpha -/- mice are shown to include gamma delta TCR+ cells that also can downregulate interferon-gamma production by the targeted CS-effector cells in vitro. Downregulation by gamma delta cells showed specificity for hapten, but was not restricted by the MHC. Together, these findings establish that gamma delta T cells cannot fulfill CS-effector functions performed by alpha beta T cells, but may fulfill an Ag-specific downregulatory role that may be directly comparable to reports of Ag-specific downregulation of IgE antibody responses by gamma delta T cells. Comparisons are likewise considered with downregulation by gamma delta T cells occurring in immune responses to pathogens, tumors, and allografts, and in systemic autoimmunity.


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