Functional and phenotypic profile of CD4+ and CD8+ T cells in Trypanosoma cruzi-infected children subjected to treatment with benznidazole

ALBAREDA MC; DE RISSIO AM; SERJAN A; TOMAS G; ALVAREZ M; FICHERA LE; ESTEVA MI; VIOTTI R; TARLETON RL; LAUCELLA S

Congreso; ASTMH 61 Annual Meeting; 2012

In this study, we sought to gain a clearer understanding of the relationship between parasite persistence and the maintenance of T. cruzi-specific T cells by examining the functional profile of T. cruzi antigen-responsive T cells and T cell phenotypes prior and after treatment with benznidazole (BZ) of 25 T. cruzi-infected children in the indeterminate phase of Chagas disease. The evaluation of the functional status of parasite-specific T cells before treatment with BZ showed that the majority of the patients display T. cruzi-antigen responsive CD4+ producing both IFN- and TNF- T cells, indicating polyfunctionality of the parasite-specific T cell compartment. Increased frequencies of terminally differentiated effector (CD45RA+CCR7–CD62L–) and effector memory (CD45RA–CCR7–CD62L–) phenotype CD4+ and CD8+ T cells were also observed in T. cruzi-infected children compared with uninfected controls. Within 8 months of treatment with BZ, the levels of total early-differentiated memory (CD45RA–CD27+CD28+) T cells increased while the levels of fully differentiated memory T cells decreased (CD45RA–CD27–CD28–) in most patients. The expression of CD127+ (IL-7 receptor) on CD4+ and CD8+ memory T cells was also increased following treatment. These changes in the phenotype of the overall T cell compartment were associated with a significant reduction in T. cruzi-specific antibodies, as assessed by conventional ELISA assays. Our results show a significant impact on the T cell compartment early after treatment with BZ which might be indicative of a reduction in parasite load after treatment of children in the indeterminate phase of Chagas disease. The high proportion of children displaying polyfunctional T cell responses specific for T. cruzi is compatible with a more competent immune status in these subjects compared with our former findings in adult T. cruzi-infected individuals, supporting our hypothesis that very long term chronic infection eventually results in T cell exhaustion.