Regulation of interleukin 2 receptor expression on murine cytotoxic T lymphocyte clones

We have previously reported that influenza virus-specific cytotoxic T lymphocyte (CTL) clones require antigen and exogenous growth factors for continued proliferation in culture. In this report we show that after stimulation with specific antigen, cloned CTL are capable of limited proliferation in response to interleukin 2 (IL 2) alone but with time these large blast-like cells revert to smaller, quiescent cells that are no longer responsive to IL 2. The IL 2-unresponsive CTL can not be driven to proliferate by supra-optimal concentrations of IL 2, and unresponsiveness correlates with decreased ability to absorb IL 2 from conditioned medium at 0 degrees C, suggesting that unresponsiveness is due to diminished IL 2 receptors. Stimulation of the unresponsive CTL with antigen leads to re-expression of the IL 2 receptor. Decreased absorbing capacity of the unresponsive cells could not be accounted for by their smaller surface area, and the IL 2-unresponsive cells seemed not to down-regulate all their immune functions, as they remained cytotoxic. These results provide a basis for the role of specific antigen in maintaining CTL clones in vitro. Furthermore, these results suggest that antigen-dependent CTL lines can be regulated and that antigen and IL 2 both play a role in their regulation.