CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
artículos
Título:
IL-6 Improves the Nitric Oxide-Induced Cytotoxic CD8+ T Cell Dysfunction in Human Chagas Disease
Autor/es:
VISCONTI L.M.; PONCE N.E.; BERNARDI G.A.; AOKI M.P.; EBERHARDT N.; SPITALE N.B.; GEA S.; SANMARCO L.M.; RAMELLO M.C.; VOZZA M.L.; MINGUEZ A.R.
Revista:
Frontiers in immunology
Editorial:
Front immunol
Referencias:
Año: 2016
Resumen:
Reactive 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 cytotoxic populationexhibited increased apoptotic rate, loss of the TCRζ-chain, and lower levels of CD107a,a marker of degranulation. Strikingly, IL-6 stimulation of in vitro-infected peripheral bloodmononuclear cells obtained from healthy donors, blunted T. cruzi-induced nitration ofCD3+CD8+ cells, and increased their survival. Furthermore, the treatment of thesecultures with an IL-6 neutralizing antibody increased the percentage of T. cruzi-inducedCD8+ T cell nitration and raised the release of nitric oxide. The results suggest that theunder-responsiveness of cytotoxic T cell population observed in the setting of long-termconstant activation of the immune system could be reverted by the pleiotropic actions ofIL-6, since this cytokine improves its survival and effector functions.