title: Inhibition of human γδ T cell proliferation and effector functions by neutrophil serine proteases.
abstract: Human peripheral blood γδ T cells expressing the Vγ9Vδ2 T cell receptor are activated by microbial or endogenous pyrophosphate antigens and indirectly by nitrogen-containing bisphosphonates. Apart from proliferation, such phosphoantigens induce proinflammatory cytokine production including TNF-α and IFN-γ and trigger cytotoxic effector function. Neutrophil granulocytes are known to modulate T cell activation. The neutrophil serine proteases proteinase 3, elastase and cathepsin G have multiple potential targets and promote microbial killing. In this study, we investigated the effect of the three serine proteases on the in vitro proliferation and effector functions of γδ T cells cultured in serum-free medium. All three proteases inhibited the proliferative activity, suppressed the cytokine production and decreased the cytotoxicity of γδ T cells. Further studies indicated that proteolytic cleavage of IL-2 and modulation of butyrophilin 3A1 (CD277) expression might contribute to the overall inhibition.
authors.affiliation: Institute of Immunology, Christian-Albrechts-University of Kiel, Kiel, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Fazio
authors.forename: S
authors.initials: S
authors.lastname: Kalyan
authors.forename: D
authors.initials: D
authors.lastname: Wesch
authors.forename: D
authors.initials: D
authors.lastname: Kabelitz
mesh_terms: D015703:Antigens, CD / Q000378:metabolism; D000071797:Butyrophilins; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000096:biosynthesis; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006801:Humans; D016130:Immunophenotyping; D007376:Interleukin-2 / Q000378:metabolism / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects / Q000276:immunology*; D009504:Neutrophils / Q000201:enzymology*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism*; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D057057:Serine Proteases / Q000378:metabolism* / Q000494:pharmacology; D016176:T-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism*
chemical_list: D015703:Antigens, CD; C558381:BTN3A1 protein, human; D000071797:Butyrophilins; D016207:Cytokines; D007376:Interleukin-2; D016692:Receptors, Antigen, T-Cell, gamma-delta; D015375:Receptors, Interleukin-2; D057057:Serine Proteases