THE EXPRESSION AND FUNCTIONALITY OF THE IL-27 RECEPTOR PATHWAY IS ASSOCIATED WITH THE LOSS OF Trypanosoma cruzi-SPECIFIC T CELLS IN PA- TIENTS WITH CHRONIC CHAGAS DISEASE

AILEN NATALE; MINNING T; ALVAREZ M. GABRIELA; VIOTTI R; BERTOCCHI GL; LOCOCO BE; ALBAREDA MC; TARLETON RL; LAUCELLA SA

Congreso; XXIX Reunión Anual de la Sociedad Argentina de Protozoología (SAP); 2017

We have previously shown that chronically T. cruzi-infected sub- jects bear several features of a process of immune exhaustion in- cluding an inverse correlation between disease severity and the magnitude of T cell responses, and alterations in the signaling path- way of the IL-7 receptor (IL-7R). Since IL-27 has a wide range of effects on T cells and like IL-7, IL-27 also exerts its function through STAT5, we evaluated the functionality of the IL-27 receptor (IL- 27R) and its association with T. cruzi-specific T cells responses. Polychromatic flow cytometry was used to analyze the expression of IL-27R components (CD130 and WSX1 chains) on CD4+ and CD8+ T cells. IL-27-dependent signaling events in T cells were also evaluated by polychromatic flow cytometry following stimulation of PBMC of chronic Chagas disease patients with recombinant human IL-27. Subjects with no signs of cardiac disease showed a signif- icant decrease in CD130+WSX1+CD4+ T cells and an increase in CD130+WSX1+CD8+ T cells compared with, either patients exhib- iting heart disease or uninfected controls. T. cruzi infection, in vitro, was able to stimulate the downregulation of the IL-27R in CD4+ T cells and the upregulation in CD8+ T cells. IL-27-induced phosphor- ylation of STAT1, STAT3 and STAT5 was lower in patients with heart disease compared with asymptomatic patients and inversely asso- ciated with the frequency of T. cruzi-specific IFN-gamma-producing T cells measured by ELISPOT assay. STAT5-downstream gene ex- pression of tbx21, eomes, gzmb and cxcl9 assessed by q-RTPCR was also reduced in patients with cardiomyopathy. These findings support a possible role of the IL-27R signaling pathway in promoting T. cruzi-specific T cells responses.