Chagasic patients are able to respond against a viral antigen from influenza virus

Abstract

Background: Trypanosoma cruzi, the etiological agent of Chagas' disease, is an obligate intracellular parasite which induces a CD8+ T cell immune response with secretion of cytokines and release of cytotoxic granules. Although an immune-suppressive effect of T. cruzi on the acute phase of the disease has been described, little is known about the capacity of CD8+ T cell from chronic chagasic patients to respond to a non-T. cruzi microbial antigen.

Methods: In the present paper, the frequency, phenotype and the functional activity of the CD8+ T cells specific from Flu-MP*, an influenza virus epitope, were determined in 13 chagasic patients and 5 healthy donors.

Results: The results show that Flu-MP* peptide specific CD8+ T cells were found with similar frequencies in both groups. In addition, Flu-MP* specific CD8+ T cells were distributed in the early or intermediate/late differentiation stages without showing enrichment of a specific sub-population. The mentioned Flu-MP* specific CD8+ T cells from chagasic patients were predominately TEM (CCR7- CD62L-), producing IL-2, IFNγ, CD107a/b and perforin, and did not present significant differences when compared with those from healthy donors.

Conclusions: Our results support the hypothesis that there is no CD8+ T cell nonspecific immune-suppression during chronic Chagas disease infection. Nonetheless, other viral antigens must be studied in order to confirm our findings.

Figure 1

Frequency of CD8⁺T cells specific for Flu-MP* peptide determined by tetramer staining. (A) Representative flow cytometry dot plot from one HLA-A*0201⁺ chagasic patient. (B) Frequency of HLA-A*0201⁺ chagasic patients (white bars) and HLA-A*0201⁺ healthy donors (grey bars). There were no statistically significant differences between healthy donors and chagasic patients P = 0.21.

Figure 2

Expression of CCR7 and CD62L in Flu-MP* peptide-specific CD8⁺T cells. (A) Phenotypic characterization by flow cytometry in one representative chagasic patient. (B) Significant differences were observed between central memory (double positive cells) T cells (T_CM) and effector memory (double negative cells) T cells (T_EM) (P < 0.008) from chagasic patients (white bars) or healthy donors (grey bars). No differences were found when the frequencies of T_CM and T_EM CD8⁺ T cells were compared between chagasic patients and healthy donors.

Figure 3

Expression of CD27 and CD28 in Flu-MP* peptide-specific CD8⁺T cells. (A) Flow cytometry dot plot of CD27 and CD28 expression in one representative chagasic patient. (B) There were no differences between the early differentiation phenotype (CD27+ CD28+) and the intermediate/late differentiation stage (CD27+ CD28-, CD27- CD28-) in CD8⁺ T cells (P > 0.151). There were no significant differences between the chagasic patients (white bars) and healthy donors (grey bars) when comparing the early phenotype (P = 0.139) with intermediate/late differentiation stage (P = 0.430).

Figure 4

Functional characterization of CD8⁺ T cells specific for Flu-MP* peptide determinated by flow cytometry. Frequency, mean fluorescence intensity (MFI) and integrated mean fluorescence intensity (iMFI) of the perforin (A), CD107a/b (B), IFNγ (C) and IL-2 (D) expression in CD8⁺ T cells specific for Flu-MP* peptide in chagasic patients (white bars) and healthy donors (grey bars). A representative dot plot of the expression of each studied molecule from one HLA-A*0201⁺ chagasic patient is shown on the right side.