Bacterial superantigens reactivate antigen-specific CD8+ memory T cells.
Superantigens stimulate naive CD4+ and CD8+ T cells in a TCR V beta-specific manner. However, it has been reported that memory T cells are unresponsive to superantigen stimulation. In this study, we show that staphylococcal enterotoxins (SE) can activate influenza virus-specific CD8+ memory cytotoxic T cells. In vivo SEB challenge of mice that had recovered from influenza virus infection (memory mice) resulted in the generation of vigorous influenza-specific cytotoxic T lymphocyte (CTL) activity and in vitro SEA or SEB stimulation of splenic T cells from memory mice, but not naive mice, also induced influenza-specific CTL. Analysis of the mechanism of activation suggested that although there may be a component of cytokine-mediated bystander activation, the CTL activity is largely generated in response to direct TCR engagement by superantigen. Moreover, influenza-specific CTL could be generated from purified CD8+ CD62L loCD44hi (memory phenotype) T cells cultured in the presence of T cell-depleted splenic antigen-presenting cells and SE. Purified CD8+ memory T cells also secreted lymphokines and synthesized DNA in response to superantigen. These results definitively demonstrate that CD8+ memory T cells respond to SE stimulation by proliferating and developing appropriate effector function. Furthermore, the data raise the possibility that otherwise inconsequential exposure to bacterial superantigens may perturb the CD8+ T cell memory pool.
Coppola
M A
MA
Department of Immunology, St Jude Children's Research Hospital, Memphis, TN 38105, USA.
Blackman
M A
MA
D000818:Animals; D000942:Antigens, Bacterial / Q000378:metabolism / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004768:Enterotoxins / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D007117:Immunization, Secondary; D007156:Immunologic Memory; D016130:Immunophenotyping; D009980:Influenza A virus / Q000276:immunology; D007274:Injections, Intraperitoneal; D007376:Interleukin-2 / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D051379:Mice; D008808:Mice, Inbred CBA; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000378:metabolism; D013211:Staphylococcus aureus / Q000276:immunology; D018089:Superantigens / Q000378:metabolism / Q000494:pharmacology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000378:metabolism
D000942:Antigens, Bacterial; D004768:Enterotoxins; D018984:Epitopes, T-Lymphocyte; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D018089:Superantigens; C026066:enterotoxin A, Staphylococcal; C031818:enterotoxin B, staphylococcal