Trypanosoma cruzi-Induced Activation of Functionally Distinct αβ and γδ CD4- CD8- T Cells in Individuals with Polar Forms of Chagas' Disease

CD4(-) CD8(-) (double-negative [DN]) T cells have recently been shown to display important immunological functions in human diseases. They express gamma delta or alpha beta T-cell receptors that recognize lipid/glycolipid antigens presented via the nonclassical major histocompatibility complex molecules of the CD1 family. We recently demonstrated that while alpha beta DN T cells serve primarily to express inflammatory cytokines, gamma delta DN T cells express mainly interleukin-10 (IL-10) in patients with cutaneous leishmaniasis. We also demonstrated a correlation between DN T cells and the expression of gamma interferon in the acute phase of Trypanosoma cruzi experimental infection. In this work, we sought to investigate whether alpha beta or gamma delta DN T cells display distinct immunoregulatory potentials in patients with polar forms of human Chagas' disease. Our data showed that in vitro infection with T. cruzi leads to expansion of DN T cells in patients with the indeterminate and severe cardiac clinical forms of the disease. However, while alpha beta DN T cells primarily produce inflammatory cytokines in both forms of the disease, gamma delta DN T cells display a marked, significant increase in antigen-specific IL-10 expression in indeterminate patients relative to cardiac patients. Finally, higher frequencies of the IL-10-producing gamma delta DN T cells were correlated with improved clinical measures of cardiac function in the patients, suggesting a protective role for these cells in Chagas' disease. Taken together, these data show distinct functional characteristics for alpha beta and gamma delta DN T cells associated with distinct morbidity rates and clinical forms in human Chagas' disease.