Trypanosoma Cruzi-Induced Activation of Functionally Distinct Alpha Beta and Gamma Delta CD4(-) CD8(-) T Cells in Individuals with Polar Forms of Chagas’ Disease


Villani, F. N. A., da Costa Rocha, M. O., Nunes, M. D. C. P., Antonelli, L. R. D. V., Magalhaes, L. M. D., dos Santos, J. S. C., … & Dutra, W. O. (2010). Trypanosoma cruzi-Induced Activation of Functionally Distinct αβ and γδ CD4− CD8− T Cells in Individuals with Polar Forms of Chagas’ Disease. Infection and immunity, 78(10), 4421-4430.


CD4 CD8 (double-negative [DN]) T cells have recently been shown to display important immunological functions in human diseases. They express γδ or αβ 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 αβ DN T cells serve primarily to express inflammatory cytokines, γδ 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 αβ or γδ 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 αβ DN T cells primarily produce inflammatory cytokines in both forms of the disease, γδ 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 γδ 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 αβ and γδ DN T cells associated with distinct morbidity rates and clinical forms in human Chagas’ disease.

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