The Journal of Experimental Medicine
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© The Rockefeller University Press, 0022-1007/1996/12/2129/ $5.00
The Journal of Experimental Medicine, Volume 184, Number 6, December 1, 1996 2129-2140

Articles

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

Marian Szczepanik*, Laurel R. Anderson{ddagger},§, Hiroko Ushio{ddagger}, Wlodzimierz Ptak*, Michael J. Owen||, Adrian C. Hayday§, and Philip W. Askenase{ddagger}

From the * Department of Immunology, College of Medicine, Jagiellonian University, Krakow, Poland; {ddagger} 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 || 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}β T cell–deficient (TCR{alpha}–/–) mice, are presented here. The results clearly show that TCR{alpha}–/– mice cannot mount CS, implicating {alpha}β T cells as the critical CS-effector cells. However, TCR{alpha}–/– 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}β 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.

Address correspondence to Philip W. Askenase, Section of Allergy and Clinical Immunology, Department of Internal Medicine, Yale University School of Medicine, 333 Cedal Street, New Haven, CT 06520-8013.

The authors are especially grateful to Scott Roberts (University of Connecticut, Storrs, CT), Topher Dudley (National Institutes of Health), and Adrian Smith (Yale University, New Haven, CT) for review of the manuscript, and to Marilyn Avallone for her excellent secretarial skills.

This work was supported by National Institutes of Health grants AI-12211, AI-26639, and AI-02174 to P.W. Askenase, and AI-27855 to A.C. Hayday, the Polish Committee of Scientific Research, Maria Sklodowska-Curie Fund II (Polish American Agreement) to W. Ptak, and the Markey Foundation to L.R. Anderson.

1Abbreviations used in this paper: DN, double negative T cells (CD4–, CD8–); CS, contact sensitivity; DTH, delayed-type hypersensitivity; MRBC, mouse red blood cells; OX, oxazolone; PCl, picryl chloride; TMB, tetramethylbenzidine; TNBSA, Trinitro-benzene sulfonic acid.


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