IL-2, IL-6, and IFN-γ have distinct effects on the IL-4 plus PMA-induced proliferation of thymocyte subpopulations

Abstract

We have previously reported complex effects of cytokine-containing T cell supernatants on the interleukin (IL)4 plus phorbol 12-myristate 13-acetate (PMA)-induced proliferative response of murine thymocytes. Here we show that recombinant murine IL-2, IL-6, and IFN-γ each differentially regulate the IL-4/PMA-driven growth of thymocyte subpopulations. Thymocytes fractionated into four subpopulations on the basis of CD4 and CD8 expression were stimulated to proliferate by IL-4/PMA. Interferon-γ (IFN-γ) caused almost complete inhibition of the CD4 +/CD8 − response but had no measurable effect on the growth of CD4 −/CD8 + or CD4 −/ CD8 − populations. This inhibitory effect was also observed on splenic CD4 +/CD8 − T cells. In contrast, IL-6 strongly enhanced the proliferative response of CD4 +/CD8 − thymocytes, but showed no effect on peripheral CD4 +/CD8 − T cells, suggesting that IL-6 may be an important regulator of growth in the thymus. IL-2 also enhanced the proliferation of both CD4 −/CD8 + and CD4 −/CD8 − thymocytes to IL-4 and PMA. To test whether the IL-4/PMA stimulus provided all the signals required to initiate growth in each subpopulation, we titrated cell number and examined the relationship between cell dose and cell response. Growth of CD8 +/CD4 − cells was cell density independent, indicating that IL-4/PMA is sufficient stimulus to induce growth of these cells. In contrast, growth of CD4 −/CD8 − and CD4 +/CD8 − cells is cell density dependent, suggesting a requirement for another signal provided by the cells themselves. These observations suggest that more signals remain to be identified in this thymocyte growth system.