Bacterial Superantigens Expand and Activate, Rather than Delete or Incapacitate, Preexisting Antigen-Specific Memory CD8+ T Cells

• Published in: The Journal of infectious diseases 2019-04, Vol.219 (8), p.1307-1317
• Main Authors: Meilleur, Courtney E, Wardell, Christine M, Mele, Tina S, Dikeakos, Jimmy D, Bennink, Jack R, Mu, Hong-Hua, McCormick, John K, Haeryfar, S M Mansour
• Format: Article
• Language: English
• Subjects: Adult; Animals; Antigens; Antigens, Bacterial - immunology; Antiviral drugs; Bacteria; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; Cell culture; Cytomegalovirus; Enterotoxins - immunology; Female; Humans; Immunologic Memory - immunology; Immunological memory; Influenza; Influenza Vaccines - immunology; Lymphocyte Activation - immunology; Lymphocytes; Lymphocytes T; Major and Brief Reports; Male; Memory cells; Mice; Mice, Inbred BALB C; Orthomyxoviridae - immunology; Peripheral blood; Phenotypes; Staphylococcal enterotoxin B; Superantigens; Superantigens - immunology; T cell receptors; Vaccination; Young Adult; γ-Interferon
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1093/infdis/jiy647

Abstract Superantigens (SAgs) released by common Gram-positive bacterial pathogens have been reported to delete, anergize, or activate mouse T cells. However, little is known about their effects on preexisting memory CD8+ T cell (TCD8) pools. Furthermore, whether SAgs manipulate human memory TCD8 responses to cognate antigens is unknown. We used a human peripheral blood mononuclear cell culture system and a nontransgenic mouse model in which the impact of stimulation by two fundamentally distinct SAgs, staphylococcal enterotoxin B and Mycoplasma arthritidis mitogen, on influenza virus– and/or cytomegalovirus-specific memory TCD8 could be monitored. Bacterial SAgs surprisingly expanded antiviral memory TCD8 generated naturally through infection or artificially through vaccination. Mechanistically, this was a T cell-intrinsic and T cell receptor β-chain variable–dependent phenomenon. Importantly, SAg-expanded TCD8 displayed an effector memory phenotype and were capable of producing interferon-γ and destroying target cells ex vivo or in vivo. These findings have clear implications for antimicrobial defense and rational vaccine design. We demonstrate that infection- and/or vaccine-elicited antiviral memory CD8+ T cells are expanded and activated by superantigens (SAgs) of distinct bacterial origin if they harbor SAg-responsive Vβ families in their T cell receptors (TCRs).