Primary activation of murine CD8 T cells via cross-linking of T3 cell surface structures: two signals regulate induction of interleukin 2 responsiveness.
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.
D000818:Animals; D000911:Antibodies, Monoclonal / Q000502:physiology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology*; D003432:Cross-Linking Reagents; D006825:Hybridomas / Q000502:physiology; D007376:Interleukin-2 / Q000378:metabolism / Q000502:physiology*; D008213:Lymphocyte Activation; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D011971:Receptors, Immunologic / Q000096:biosynthesis / Q000276:immunology / Q000502:physiology; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000145:classification* / Q000276:immunology
D000911:Antibodies, Monoclonal; D000945:Antigens, Differentiation, T-Lymphocyte; D003432:Cross-Linking Reagents; D007376:Interleukin-2; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2