Interleukin-2 Induced Mitogenesis of Human Peripheral Blood T-Lymphocytes: Role of Accessory Cells

Abstract

We and others have shown that interleukin-2 (IL-2) is mitogenic to a subset of unstimulated T lymphocytes in human peripheral blood (1-7). We extend our work here in showing that prolonged continuous exposure of human peripheral blood lymphocytes to exogenous IL-2 throughout the 7-8 day culture is not necessary since mitogenesis occurs reproducibly after short term (2-3 hr) pulse exposure. The mitogenic effect of pulse exposure to IL-2 is not significantly reduced by inclusion of anti-Tac monoclonal antibody in the pulsing medium. However, anti-Tac monoclonal antibody markedly inhibits the response if present continuously throughout the 7 day culture. The mitogenic effect of IL-2 is dependent on the presence of accessory cells (monocytes) but the accessory cell requirement can be replaced by the phorbol ester TPA (10(-8 to 10(-11) M). Purified monocytes subjected to short term pulse exposure to IL-2 can cause proliferative response in unprimed autologous lymphocytes in co-cultures. The mitogenic effect of IL-2 pulsed monocytes can not be suppressed by inclusion of anti-Tac antibody in the pulsing medium although the same concentration of the antibody suppresses the effect if present throughout culture. The response of lymphocytes to IL-2 pulsed monocytes is not inhibitable by the continuous presence of a monoclonal antibody to human HLA-DR antigens (OK-Ia1) in culture.