Regulation of the immune response by subclasses of T lymphocytes. I. Interactions between pre-killer T cells and regulatory T cells obtained from peripheral lymphoid tissues of mice.

The generation of killer cells to alloantigens in vitro depends upon an interaction between two subclasses of peripheral T cells: "pre-killer" T cells and "regulatory" T cells. The pre-killer T cell, found in highest concentrations in peripheral lymph nodes of mice, is sensitive in vivo to the administration of small doses of anti-thymocyte serum (ATS) and is depleted in vitro by treatment with (a) anti-Thy-1.2 + C, (b) low doses (600 r) of x-irradiation. Specificity of pre-killer cells is supported by adsorption of pre-killer activity on appropriate allogeneic monolayers and by the specific absence of this activity from lymphoid tissues of mice rendered tolerant in neonatal life. Although T cells remaining in the spleen 2 days after a small dose of ATS (SPA-T) did not generate killer cells, this subset exerted substantial regulatory effects upon the generation of killer activity by pre-killer T cells. The addition of this population of regulatory T cells to small numbers of lymph node T cells (LN-T) resulted in substantial enhancement in the generation of killer cells from the LN-T pre-killers. The addition of SPA-T to larger numbers of LN-T (which produce strong responses alone), failed to enhance the response, and in some cases resulted in significant suppression which could not easily be accounted for by alteration in cell numbers in culture. Although amplifier activity was relatively radioresistant, "suppressor" activity was sensitive to relatively small doses of irradiation. The significance of this T-T interaction is discussed.