Polyfunctional CD4+ T cells specific for Trypanosoma cruzi can be restored after in vitro treatment with IL-7 and IL-27

Abstract

Abstract Chronically Trypanosoma cruzi-infected subjects bear several features associated with immune exhaustion, including an impairment in the polyfunctionality of T cells over time and alterations in the IL-7/IL-7R and IL-27/IL-27R axis. Since IL-7 and IL-27 have several functions on different immune cells, gene expression analysis was conducted in total PBMCs in response to rhIL-7 and rhIL-27 in vitro. TBX21, EOMES, GZMB and MIG-cytokine-induced gene expression was low in patients with severe Chagas disease compared with those without cardiac involvement. IL-7-induced TBX21 expression positively correlated with the magnitude of T. cruzi-specific T-cell responses. We also assessed whether treatment of PBMCs of chronically T. cruzi infected subjects with IL-7/IL-27 could improve the quality of T. cruzi-specific T-cell responses. Polyfunctionality of CD4+ T cells was improved after treatment with IL-7 and IL-27, by increasing the production of IL-2 on CD4+ T cells producing two or three functions in response to T. cruzi antigens in patients with mild cardiac disease. These findings support that alterations in IL-7/IL-27 pathways in chronic Chagas disease are not only at the signal-transduction level but also at the transcriptional regulation level. In vitro treatment of PBMCs of patients in early clinical stages of chronic Chagas disease can restore T-cell function.