Chagas disease is a persistent parasitic infection that does not induce sterilizing immunity. The generation of memory T cell response depends on the environmental conditions at the initial antigenic priming . Indeed, the T cell responses may be influenced by previous antigen encounters, a phenomenon known as “original antigenc sin” . Thus, the goal of this study was to determine whether chagasic patients are able to respond against a non-T. cruzi microbial antigen such as the matrix peptide derived from influenza virus. Exposure to influenza virus is widely spread therefore most individuals develop a serotype-dependent sterilizing immunity.
At first, frequency of Flu-MP* peptide-specific CD8+ T cells from chronic chagasic patients and healthy donors was studied. Noticeably, no differences were found between these two groups. Moreover, the average frequency values were similar to those previously reported for the influenza-M158–66 (GILGFVFTL) specific CD8+ T cells (0.28% to 0.73%) from healthy donors . A similar Flu-MP tetramer positive cell frequency (0.11% to 0.56%) was reported in six HLA-A*0201+ healthy donors . Likewise, in a previous study we reported the existence of Flu-MP*-specific CD8+ T cells with frequencies up to 0.36% in 16 out of 19 HLA-A2+ chagasic patients and frequencies up to 0.25% in 10 out of 12 healthy donors without statistically significant difference when non-chagasic and T. cruzi infected individuals were compared (P > 0.05) .
Memory T cells consist in central (TCM) and effector (TEM) memory cells [28, 30, 35]. While human TCM express CCR7 and CD62L, molecules involved in cellular homing to lymphoid tissue, human TEM have lost the expression of CCR7 and CD62L and preferentially migrate to non-immune tissues . In this study, Flu-MP* peptide-specific CD8+ T cells were predominately TEM cells, in both healthy donors and chagasic patients. Results that are in agreement with reports of Hoji et al., showing that Flu-specific T cells from healthy donors had a lower proportion of CCR7 expression on Flu-specific T cells and a moderate expression of CD62L with a phenotype that corresponds to effector memory CD8+ T cells . Expression of CD27 and CD28 are useful in distinguishing CD8+ T cell differentiation stages: early (CD27+ CD28+), intermediate (CD27+ CD28-) and late differentiation (CD27- CD28-) . In our study, in the influenza-specific CD8+ T cells there was not a predominant population based on CD27 and CD28 expression. During chronic viral infection, and depending on the infecting virus, there is a certain predominance of a cell stage of differentiation . Nonetheless, we could not find any report in the literature showing the expression of these markers in influenza-specific CD8+ T cells to be compared with our results.
CD8+ TEM cells have cytotoxic granules and produce cytokines within hours after antigenic stimulation. MP-Flu* peptide-specific CD8+ T cells expressed surface CD107a/b and were able to secrete IL-2, IFNγ and storage perforin. Interestingly, in both infected patients and healthy donors, the expression of IL-2, IFNγ and perforin by Flu-MP* peptide-specific CD8+ T cells was similar in magnitude (percentage of expressing cells), quality (MFI) or both (iMFI), indicating that these populations are equally functional upon Flu-MP* peptide recognition.
In agreement with results presented here, a study of congenital Chagas disease performed in newborns congenitally infected with T. cruzi, showed that the infection did not interfere with responses to Bacillus Calmette Guerin (BCG), hepatitis B, diphtheria, and tetanus vaccines during the neonatal period .