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.
Kalyan
Shirin
S
Division of Infectious Diseases, Departments of Medicine, Microbiology and Immunology, University of British Columbia and Vancouver Hospital Coastal Health Research Institute, Vancouver, BC, Canada.
Chow
Anthony W
AW
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