Evidence of polyfunctional T cell responses in subjects exposed to Trypanosoma cruzi

ALBAREDA C; ALVAREZ MG ; PEREZ-MAZLIAH D; ARMENTI A; VIOTTI R; COOLEY G; LAUCELLA S; TARLETON RL

Banff, Alberta

Simposio; Keystone symposium:Immunologic Memory, Persisting Microbes and Chronic Disease; 2011

We previously reported that T cell responses specific for T. cruzi in chronically infected humans display a functional profile with T cells secreting interferon-g alone as the predominant pattern and very low prevalence of dual IFN-g/IL-2 secreting T cells, denoting a lack of polyfunctional responses characteristic of long-term antigen stimulation. A subject is considered infected with T. cruzi when at least 2 out of 3 conventional serological tests (immunofluorescence, ELISA and hemagglutination) are positive. Subjects with only 1 of 3 positive tests are regarded as “discordant”, irrespective of other risk factors and clinical evidence of T. cruzi infection. This study aimed to evaluate the frequencies of polyfunctional (e.g. IFN-g and IL-2 secreting) T cells in subjects with discordant serology to investigate the possibility that these subjects were exposed to but are not currently infected with T. cruzi and thus retained T cell memory specific for T. cruzi. Ten subjects with discordant conventional serological tests and 5 seronegative subjects born in areas endemic for T. cruzi-infection but who have lived in non-endemic areas for more than 20 years were included in the analysis. Ten seronegative subjects born in non-endemic areas were also included as negative controls. IFN-g and IL-2 secreting T cells were measured by ELISPOT after stimulation of peripheral blood mononuclear cells with T. cruzi antigens. Eight out of the 10 (80%) subjects with discordant serology and 1 out of the 5 seronegative subjects (20%) from T. cruzi endemic areas had both positive IFN-g and IL-2 T cell responses specific for T. cruzi, while none of the seronegative subjects from non-endemic areas had positive T cell responses. These findings of polyfunctional T cells in a majority of subjects with questionable serology contrasts with in the low percentage of subjects with polyfunctional T cells among those who have strong serological responses ( less than 25%; Alvarez, 2008). These results suggest a differential T cell memory response in some T. cruzi exposed subjects that could be a reflection of cleared infections.