Activation of virus specific CTL clones: antigen-dependent regulation of interleukin 2 receptor expression.

Abstract

Interleukin 2 (IL 2) is a lymphocyte-specific growth hormone, whose effect on lymphocyte proliferation is exerted through a cell surface receptor expressed on activated lymphocytes. In this report we have used monoclonal antibodies directed to the murine IL 2 receptor to examine the regulation of the IL 2 receptor expression on cloned populations of influenza virus-specific CTL. The CTL clones, which are dependent on both specific antigenic stimulation and exogenous IL 2 for continuous in vitro propagation, express high levels of the IL 2 receptor shortly after antigenic stimulation (day 2 or 3). Over the next 5 to 8 days of in vitro cultivation in IL 2-containing medium, these cloned CTL cells express decreasing levels of IL 2 receptor. Concomitant with this fall in IL 2 receptor expression, the cells become refractory to the IL 2 proliferative stimulus. The cloned cells remain refractory to IL 2 until specifically stimulated by antigen, which induces high levels of the IL 2 receptor on the cells and renders the cells sensitive to IL 2 once again. These results support the concept that IL 2 receptor expression on activated T lymphocytes is transitory and that receptor expression is endogenously regulated in the activated T lymphocytes. These results also suggest that antigen plays a primary role in regulating T lymphocyte proliferation by maintaining IL 2 receptor levels.