Peptide antigen priming of naive, but not memory, CD8 T cells requires a third signal that can be provided by IL-12.
Challenge with peptide Ag in the absence of adjuvant results in tolerance of CD8 T cells specific for the Ag. In contrast, administration of IL-12 along with peptide results in massive clonal expansion, development of effector function, and establishment of a long-lived memory population. Using adoptive transfer of TCR-transgenic CD8 T cells, this effect of IL-12 is shown to be independent of CD4 T cells and to require costimulation provided by CD28 and possibly LFA-1. IL-12 supports responses when IL-12Rbeta1-deficient mice are used as recipients for the adoptively transferred CD8 T cells, demonstrating that the IL-12 is acting directly on the T cells rather than on host APC. These results provide strong support for a three-signal model for in vivo activation of naive CD8 T cells by peptide Ag, in which the presence or absence of the third signal determines whether tolerance or activation occurs. In contrast, memory CD8 T cells are effectively activated by peptide Ag in the absence of IL-12 or adjuvant.
Schmidt
Clint S
CS
Center for Immunology, Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Mescher
Matthew F
MF
D000069594:Abatacept; D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000276:immunology*; D015703:Antigens, CD; D000943:Antigens, Differentiation / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D060908:CTLA-4 Antigen; D003713:Dendritic Cells / Q000502:physiology; D018796:Immunoconjugates; D007156:Immunologic Memory; D018799:Intercellular Adhesion Molecule-1 / Q000502:physiology; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL
D000941:Antigens; D015703:Antigens, CD; D000943:Antigens, Differentiation; D060908:CTLA-4 Antigen; C556707:Ctla4 protein, mouse; D018796:Immunoconjugates; D007376:Interleukin-2; D018799:Intercellular Adhesion Molecule-1; D018664:Interleukin-12; D000069594:Abatacept