IL-6 Improves the Nitric Oxide-Induced Cytotoxic CD8+ T Cell Dysfunction in Human Chagas Disease

SANMARCO L.M.; VISCONTI L.M.; EBERHARDT N.; RAMELLO M.C.; PONCE N.E.; SPITALE N.B.; VOZZA M.L.; BERNARDI G.A.; GEA S.; MINGUEZ A.R.; AOKI M.P.

Frontiers in immunology

Front immunol

Año: 2016

eactive oxygen and nitrogen species are important microbicidal agents and are alsoinvolved in lymphocyte unresponsiveness during experimental infections. Many of thebiological effects attributed to nitric oxide are mediated by peroxynitrites, which inducethe nitration of immune cells, among others. Our group has demonstrated that nitricoxide is involved in the suppressive activity of myeloid-derived suppressor cells inTrypanosoma cruzi-infected mice, with a higher number of CD8+ T cells suffering surface-nitrationcompared to uninfected controls. Studying the functional and phenotypicfeatures of peripheral CD8+ T cells from chagasic patients and human cells experimentallyinfected with T. cruzi, we found that different regulatory mechanisms impaired theeffector functions of T cytotoxic population from seropositive patients. Peripheral leukocytesfrom chagasic patients showed increased nitric oxide production concomitantwith increased tyrosine nitration of CD8+ T cells. Additionally, this