The generation of memory antigen-specific cytotoxic T cell responses by CD28/CD80 interactions in the absence of antigen.
The interaction of co-stimulatory molecules CD80/CD86 on antigen-presenting cells with CD28 on naive CD8+ cytotoxic T (Tc) cells is understood to be critical in the induction of Tc effectors. CD80 is capable of providing signal 2 for the activation of Tc cells, but has no effect if encountered in the absence of specific peptide/MHC complexes (signal 1). We have found that CD80 presented in vitro to resting memory viral-immune or alloimmune Tc cells can provide sufficient stimulus for the generation of effector Tc cells in the absence of specific antigen, the peptide/MHC class I complex. Effector Tc cells generated in vitro from influenza- or class I alloantigen-primed mice by co-stimulation in the absence of antigen require exogenous interleukin (IL)-2 signaling via the cell surface-expressed IL-2 receptor or, under conditions of IL-2 blockade, exogenous IL-7. Activation of memory Tc cells by signal 1 and 2 is independent of IL-2 and IL-7. Although memory influenza-immune Tc cells did respond to CD80 in the absence of antigen, the presence of antigen +CD80 enabled an earlier induction of these Tc cells and they retained their lytic activity in vitro over a longer time period. The capacity of memory Tc cells to be activated by signal 2 alone provides one explanation for the observed heterogeneity of phenotype of memory T cells in vivo and a possible mechanism for the maintenence of memory in the absence of persisting antigen.
Flynn
K
K
Division of Immunology and Cell Biology, John Curtin School of Medical Research, Australian National University, Canberra.
Müllbacher
A
A
D000818:Animals; D000956:Antigens, Viral / Q000032:analysis* / Q000276:immunology*; D018122:B7-1 Antigen / Q000494:pharmacology*; D018106:CD28 Antigens / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects* / Q000276:immunology; D004357:Drug Synergism; D007156:Immunologic Memory / Q000187:drug effects* / Q000276:immunology*; D009980:Influenza A virus / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology; D014616:Vaccinia virus / Q000276:immunology
D000956:Antigens, Viral; D018122:B7-1 Antigen; D018106:CD28 Antigens