Bacterial superantigens reactivate antigen-specific CD8+ memory T cells

• Published in: International immunology 1997-09, Vol.9 (9), p.1393-1403
• Main Authors: Coppola, M A, Blackman, M A
• Format: Article
• Language: English
• Subjects: Animals; Antigens, Bacterial - metabolism; Antigens, Bacterial - pharmacology; Cytotoxicity, Immunologic - drug effects; Enterotoxins - administration & dosage; Enterotoxins - metabolism; Enterotoxins - pharmacology; Epitopes, T-Lymphocyte - immunology; Immunization, Secondary; Immunologic Memory; Immunophenotyping; Influenza A virus - immunology; Injections, Intraperitoneal; Interleukin-2 - pharmacology; Lymphocyte Activation - drug effects; Mice; Mice, Inbred CBA; Mice, Transgenic; Receptors, Antigen, T-Cell, alpha-beta - metabolism; Staphylococcus aureus - immunology; Superantigens - metabolism; Superantigens - pharmacology; T-Lymphocytes, Cytotoxic - immunology; T-Lymphocytes, Cytotoxic - metabolism
• ISSN: 0953-8178; 1460-2377; 1460-2377
• DOI: 10.1093/intimm/9.9.1393

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.