Primary activation of murine CD8 T cells via cross-linking of T3 cell surface structures: two signals regulate induction of interleukin 2 responsiveness.

Abstract

In the model system used here to study the minimal signal requirements for the activation of murine resting CD8 T cells, cross-linking of T cell receptor structures by antigen-presenting cells is substituted for by the use of anti-CD3 monoclonal antibodies immobilized in Sepharose beads. We show that cross-linking of CD3 structures, even in combination with CD8 structures, is necessary but insufficient to induce responsiveness to the growth-promoting effect of interleukin 2 (IL2), i.e. fails to induce expression of functional IL2 receptors. A macrophage cell line product termed IL2 receptor-inducing factor (RIF), but not IL1, IL3, IL4 or tumor necrosis factor, efficiently functions as costimulator. Once activated, growth of CD8 T cells is entirely driven by IL2. We conclude that two restriction points control the activation of resting CD8 T cells. While cross-linking of CD3 structures is essential as a first step, RIF is required as competence factor to induce IL2 responsiveness. We consider the possibility that the ability of antigen-presenting cells to produce RIF determines the immunogenicity of presented antigen towards antigen-reactive resting CD8 T cells.