Modulation of gamma delta T-cell activation by neutrophil elastase

作者：Yasmin Towstyka Nadia; Maiumi Shiromizu Carolina; Keitelman Irene; Sabbione Florencia; Veronica Salamone Gabriela; Raul Geffner Jorge; Silvina Trevani Analia; Cristina Jancic Carolina

来源：Immunology, 2018, 153(2): 225-237.

DOI：10.1111/imm.12835

• elastase
• neutrophil serine proteases
• neutrophils
• protease-activated receptor
• gamma delta T cells

gamma delta T cells are non-conventional, innate-like T cells, characterized by a restricted T-cell receptor repertoire. They participate in protective immunity responses against extracellular and intracellular pathogens, tumour surveillance, modulation of innate and adaptive immune responses, tissue healing, epithelial cell maintenance and regulation of physiological organ function. In this study, we investigated the role of neutrophils during the activation of human blood gamma delta T cells through CD3 molecules. We found that the up-regulation of CD69 expression, and the production of interferon-gamma and tumour necrosis factor-alpha induced by anti-CD3 antibodies was potentiated by neutrophils. We found that inhibition of caspase-1 and neutralization of interleukin-18 did not affect neutrophil-mediated modulation. By contrast, the treatment with serine protease inhibitors prevented the potentiation of gamma delta T-cell activation induced by neutrophils. Moreover, the addition of elastase to gamma delta T-cell culture increased their stimulation, and the treatment of neutrophils with elastase inhibitor prevented the effect of neutrophils on gamma delta T-cell activation. Furthermore, we demonstrated that the effect of elastase on T cells was mediated through the protease-activated receptor, PAR1, because the inhibition of this receptor with a specific antagonist, RWJ56110, abrogated the effect of neutrophils on gamma delta T-cell activation.

• 出版日期2018-2