Inhibitory receptor expression on CD8+ T cells is linked to functional responses against trypanosoma cruzi antigens in chronic chagasic patients

Paola Lasso, Jose Mateus, Paula Pavía, Fernando Rosas, Nubia Roa, M. Carmen Thomas, Manuel C. López, John M. González, Concepción J. Puerta, Adriana Cuéllar

Research output: Contribution to journalArticlepeer-review

50 Scopus citations

Abstract

In mammals, chronic diseases resulting from infectious agents have been associated with functional T cell response deficiency, a high frequency of terminally differentiated T cells, the presence of monofunctional Ag-specific T cells, and increased expression of inhibitory receptors. Similar to other chronic diseases, the progressive loss of certain functional activities during Trypanosoma cruzi infection might result in the inability to control replication of this parasite. To examine this hypothesis, we evaluated the differentiation and cell effector function of CD8+ T cells and characterized the expression of inhibitory receptors and the presence of the parasite in the bloodstream of chagasic patients. The results showed that patients at an advanced severe disease stage had a higher frequency of terminally differentiated CD8+ T cells than patients at an early stage of the disease. A monofunctional CD8+ T cell response was observed in patients at an advanced stage, whereas the coexpression of markers that perform three and four functions in response to parasite Ags was observed in patients at a less severe disease stage. The frequency of CD8+ T cells producing granzyme B and perforin and those expressing inhibitory receptors was higher in symptomatic patients than in asymptomatic patients. Taken together, these findings suggest that during the course of Chagas disease, CD8+ T cells undergo a gradual loss of function characterized by impaired cytokine production, the presence of advanced differentiation, and increased inhibitory receptor coexpression.

Original languageEnglish
Pages (from-to)3748-3758
Number of pages11
JournalJournal of Immunology
Volume195
Issue number8
DOIs
StatePublished - 15 Oct 2015
Externally publishedYes

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