Bacterial Superantigens Expand and Activate, Rather than Delete or Incapacitate, Preexisting Antigen-Specific Memory CD8+ T Cells. (12th November 2018)

• Record Type: Journal Article
• 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
• Is Part Of: Journal of infectious diseases. Volume 219:Number 8(2019)
• Page Start: 1307
• Page End: 1317
• Publication Date: 2018-11-12
• Subjects: Staphylococcus aureus -- superantigen -- staphylococcal enterotoxin B -- Mycoplasma arthritidis mitogen -- influenza -- cytomegalovirus -- T cell repertoire -- TCD8 -- cytotoxicity -- immunological memory; Communicable diseases -- Periodicals; Diseases -- Causes and theories of causation -- Periodicals; Medicine -- Periodicals; Communicable Diseases -- Periodicals; Electronic journals; 616.9
• DOI: 10.1093/infdis/jiy647
• Languages: English
• ISSNs: 0022-1899

Abstract

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. Abstract : 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).