γδ T Cells from Tolerized αβ T Cell Receptor (TCR)–deficient Mice Inhibit Contact Sensitivity-Effector T Cells In Vivo, and Their Interferon-γ Production In Vitro

Abstract

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 αβ T cell–deficient (TCRα−/−) mice, are presented here. The results clearly show that TCRα−/− mice cannot mount CS, implicating αβ T cells as the critical CS-effector cells. However, TCRα−/− mice can, after high dose tolerance, downregulate α+/+ 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 α−/− mice are shown to include γδ TCR+ cells that also can downregulate interferon-γ production by the targeted CS-effector cells in vitro. Downregulation by γδ cells showed specificity for hapten, but was not restricted by the MHC. Together, these findings establish that γδ T cells cannot fulfill CS-effector functions performed by αβ 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 γδ T cells. Comparisons are likewise considered with downregulation by γδ T cells occurring in immune responses to pathogens, tumors, and allografts, and in systemic autoimmunity.