Effect of urate monosodium crystals on gamma/delta T cells

TOWSTYKA, NADIA YASMÍN; SABBIONE, FLORENCIA; GEFFNER, JORGE; TREVANI, ANALÍA; JANCIC, CAROLINA

Buenos Aires

Congreso; 63 Reunión Anual de la Sociedad Argentina de Inmunología. 2da FAIC; 2015

Sociedad Argentina de Inmunología - LASID

Background:Uric acid is the final product of purine metabolismin humans and higher primates. It is released from dying cells and function asan adjuvant that promotes the generation of adaptive immune responses. Theinflammatory effect of uric acid depends on its precipitation into monosodiumurate (MSU) crystals. MSU crystals could be recognized by dendritic cells,macrophages, and neutrophils. Moreover, antigen-presenting cells can sense uricacid as a proinflammatory endogenous signal released by damaged cells/tissues. Gamma/delta T cells constitute a specialized subset of Tlymphocytes, which act as early sensors of cellular stress and infection. Wehypothesized that uric acid released from dying cells might function as aproinflammatory danger signal on gamma/delta Tcells. Then, neutrophils located in injured tissues could influence gamma/delta Tcell functions. Methods:gamma/delta T cells were purified from human peripheral bloodby using anti-TCR gamma/delta MicroBeadisolation kit, and neutrophils by dextran sedimentation. Purified gamma/delta T cells were incubated with MSU crystals (12.5-300 microg/ml) withor without neutrophils. After 48 hours, we analyzed cytokines production insupernatants by ELISA. Results: MSUcrystals induced an increase in TNF-alpha, IFN-gamma, IL-6 and IL-8 production (p<0.05, n=3) and did not alter gamma/delta Tcell viability. In presence of MSU crystals, neutrophils interact with gamma/delta Tcells more efficiently and impede gamma/delta Tcell cytokine production (p<0.05, n=3). Conclusion: Ourresults suggest that gamma/delta Tcells could sense the presence of MSU crystals, playing a role during celldeath-induced inflammation. This event could be regulated by neutrophils.