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 areunresponsive to superantigen stimulation. In this study, we show thatstaphylococcal enterotoxins (SE) can activate influenza virus-specific CD8+memory cytotoxic T cells. In vivo SEB challenge of mice that had recoveredfrom influenza virus infection (memory mice) resulted in the generation ofvigorous influenza-specific cytotoxic T lymphocyte (CTL) activity and invitro SEA or SEB stimulation of splenic T cells from memory mice, but notnaive mice, also induced influenza-specific CTL. Analysis of the mechanismof activation suggested that although there may be a component ofcytokine-mediated bystander activation, the CTL activity is largelygenerated 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-depletedsplenic antigen-presenting cells and SE. Purified CD8+ memory T cells alsosecreted lymphokines and synthesized DNA in response to superantigen. Theseresults definitively demonstrate that CD8+ memory T cells respond to SEstimulation by proliferating and developing appropriate effector function.Furthermore, the data raise the possibility that otherwise inconsequentialexposure to bacterial superantigens may perturb the CD8+ T cell memorypool.