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Background  Subjects are considered infected with  Trypanosoma cruzi  when tested positive by at least two out of three serological tests, whereas a positive result in only one of up to three tests is termed “serodiscordant” (SD). Assessment of parasite-specific T-cell responses may help discriminate the uninfected from infected individuals among SD subjects.    Methods  Peripheral blood mononuclear cells from SD and seropositive (SP) subjects, who were born in areas endemic for  T. cruzi  infection but living in Buenos Aires city, Argentina, at the time of the study, and seronegative unexposed subjects were included for analysis. The function and phenotype of T cells were assessed by interferon-γ (IFN-γ) and interleukin (IL)-2 enzyme-linked immunospot assay and multiparameter flow cytometry.  T. cruzi -specific antibodies were quantified by conventional serology and a multiplex assay format.    Results  SD subjects exhibited immunity cell responses to  T. cruzi  but in contrast to SP subjects, T cells in SD subjects more often display the simultaneous production of IFN-γ and IL-2 in response to  T. cruzi  antigens and have a resting phenotype. SD individuals also have higher IFN-γ spot counts, polyfunctional CD4 +  T-cells enriched in IL-2 secreting cells and low levels of antibodies specific for a set of  T. cruzi -derived recombinant proteins compared with the SP group. Long-term follow-up of SD individuals confirmed that humoral and T-cell responses fluctuate but are sustained over time in these subjects. T cells in SD subjects for  T. cruzi  infection did not recognize  Leishmania  antigens.    Conclusion  Both T-cell and humoral responses in most subjects assessed by conventional tests as SD for  T. cruzi  infection indicate prior exposure to infection and the establishment of immunological memory suggestive of a resolved infection.

The Significance of Discordant Serology in Chagas Disease: Enhanced T-Cell Immunity to Trypanosoma cruzi in Serodiscordant Subjects