Linking innate and adaptive immunity: human Vgamma9Vdelta2 T cells enhance CD40 expression and HMGB-1 secretion.
gammadelta T cells play an important role in regulating the immune response to stress stimuli; however, the mean by which these innate lymphocytes fulfill this function remains poorly defined. The main subset of human peripheral blood gammadelta T cells responds to nonpeptidic antigens, such as isopentylpyrophosphate (IPP), a metabolite in the mevalonate pathway for both eukaryote and prokaryote cells. IPP-primed gammadelta T cells significantly augment the inflammatory response mediated by monocytes and alphabeta T cells to TSST-1, the staphylococcal superantigen that is the major causative agent of toxic shock syndrome. Here we show that the small pool of activated peripheral gammadelta T cells induces an early upregulation of CD40 on monocytes and the local release of High Mobility Group Box-1 (HMGB-1), the molecule designated as the late mediator of systemic inflammation. This finding provides a new basis for how gammadelta T cells may serve as influential modulators of both endogenous and exogenous stress stimuli.
Division of Infectious Diseases, Departments of Medicine, Microbiology and Immunology, University of British Columbia and Vancouver Hospital Coastal Health Research Institute, Vancouver, BC, Canada.
Shirin
S
Kalyan
Anthony W
AW
Chow
D056704:Adaptive Immunity / Q000276:immunology*; D000818:Animals; D001427:Bacterial Toxins / Q000276:immunology; D018106:CD28 Antigens / Q000276:immunology; D019013:CD40 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D004768:Enterotoxins / Q000276:immunology; D024243:HMGB1 Protein / Q000276:immunology / Q000378:metabolism*; D006801:Humans; D007113:Immunity, Innate / Q000276:immunology*; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008213:Lymphocyte Activation; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology; D018089:Superantigens / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*
D001427:Bacterial Toxins; D018106:CD28 Antigens; D019013:CD40 Antigens; D004768:Enterotoxins; D024243:HMGB1 Protein; D053645:Interleukin-2 Receptor alpha Subunit; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018089:Superantigens; C030107:enterotoxin F, Staphylococcal