INVOLVEMENT OF TNF IN THE ACTIVATION OF GAMMA DELTA T LYMPHOCYTES BY HUMAN GLOMER- ULAR NVOLVEMENT OF TNF- IN THE ACTIVATION OF GAMMA DELTA T LYMPHOCYTES BY HUMAN GLOMER- ULAR ENDOTHELIAL CELLS EXPOSED TO SHIGA TYPE 2 TOXIN. ROLE IN THE PATHOGENESIS OF

ROSSO DAVID A; ROSATO MICAELA; GOMEZ FERNANDO D; ALVAREZ ROMINA; SHIROMIZU CAROLINA; IBARRA CRISTINA; AMARAL MARÍA MARTA; JANCIC CAROLINA

Congreso; Reunión de Sociedades de Biociencias.; 2021

Sociedad Argentina de Investigación Clínica

The hemolytic uremic syndrome US associated with diarrhea,a consequence of Shiga toxin (Stx)-producing Escherichia coli in-fection, is a common cause of pediatric acute and chronic renalfailure. Stx type 1 and type 2 (Stx1 and Stx2) produced by thosebacteria are the main factors related with HUS that trigger kidneydamage. Stx2-producing strains are associated with severe casesof HUS in Argentina. gd T cells are a specialized subset of T lym-phocytes, which act as early sensors of cellular stress and infection.They can exert cytotoxicity against infected and transformed cellsand produce cytokines and chemokines. In this work, we studiedthe activation of human peripheral gd T cells in response to humanglomerular endothelial cells EC exposed to Stx2 0.01 ng/ml,24 h or their conditioned medium. e analyzed CD69, CD107a,and perforin expression by ow cytometry and cytokine productionby ELISA and intracellular staining in gd T cells after incubation withStx2-treated EC or their conditioned medium. e evaluated byconfocal microscopy, the interaction between gd T cells and ECtreated or not with Stx2 and perforin distribution. As result, we ob-served an increase in TNF- , IFN- , and cell interactions p<0.05)in gd T cells cultured with Stx2-treated EC, and perforin polariza-tion but without changes in CD69. Moreover, gd T cells incubatedwith Stx2-treated EC conditioned medium showed an increasein TNF- and IFN- production, and CD107a expression and a de-crease in intracellular perforin (p 0.05 . Interestingly, the blockageof TNF-a by Etanercept reverted the increase in TNF-a, IFN-g, andCD107a, and the decrease in perforin p<0.05) in gd T cells incubat-ed with Stx2-treated EC conditioned medium. Our results indicate that soluble factors released by Stx2-stimulated EC modu-late the activation of gd T cells, being TNF-a a key player during thisprocess. This suggest that gd T cells could be involved in the renalendothelial damage in SUH.