Premium
Inhibition of Human γδ T Cell Proliferation and Effector Functions by Neutrophil Serine Proteases
Author(s) -
Fazio J.,
Kalyan S.,
Wesch D.,
Kabelitz D.
Publication year - 2014
Publication title -
scandinavian journal of immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.934
H-Index - 88
eISSN - 1365-3083
pISSN - 0300-9475
DOI - 10.1111/sji.12221
Subject(s) - proteases , cathepsin g , neutrophil elastase , effector , cytotoxic t cell , proinflammatory cytokine , elastase , biology , microbiology and biotechnology , cytokine , chemistry , in vitro , biochemistry , immunology , inflammation , enzyme
Human peripheral blood γδ T cells expressing the V γ 9 V δ 2 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 3 A 1 ( CD 277) expression might contribute to the overall inhibition.