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

Contact sensitivity (CS) responses to reactive hapten Ag, such as picr yl chloride (PCl) or oxazolone (OX), are classical examples of T cell- mediated immune responses in vivo that are clearly subject to multifac eted 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 re sponses and mediate their downregulation, we have undertaken studies o f CS in mice congenitally deficient in specific subsets of lymphocytes . The first such studies, using alpha beta T cell-deficient (TCR alpha (-/-)) mice, are presented here. The results clearly show that TCR alp ha(-/-) mice cannot mount CS, implicating alpha beta T cells as the cr itical CS-effector cells. However, TCR alpha(-/-) mice can, after high dose tolerance, downregulate alpha(+/+) CS-effector T cells adoptivel y transferred into them. By mixing ex vivo and then adoptive cell tran sfers in vivo, the active downregulatory cells in tolerized alpha(-/-) mice are shown to include gamma delta TCR(+) cells that also can down regulate 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 es tablish that gamma delta T cells cannot fulfill CS-effector functions performed by alpha beta T cells, but may fulfill an Ag-specific downre gulatory role that may be directly comparable to reports of Ag-specifi c downregulation of IgE antibody responses by gamma delta T cells. Com parisons are likewise considered with downregulation by gamma delta T cells occurring in immune responses to pathogens, tumors, and allograf ts, and in systemic autoimmunity.