Treatment of chronically Trypanosoma cruzi infected subjects with benznidazole induces a transient increase in T. cruzi-specific memory T cells with characteristics of short-lived T cells.

LAUCELLA SA; PÉREZ D; ALVAREZ MG; BERTOCCHI G; ALBAREDA MC; VIOTTI R; POSTAN M; ARMENTI A; TARLETON RL

Philadelphia, USA

Congreso; American Society of Tropical Medicine and Hygiene 56th Annual Meeting.; 2007

We have studied the change in T. cruzi-specific T cell responses following treatment of chronic chagasic subjects with benznidazole (BZ). In comparison to untreated subjects, who generally show a stable level of IFN-g-producing memory T cells specific for T. cruzi, a significant proportion of BZ-treated subjects exhibit an initial increase in IFN-g responses between 2 or 6 months post treatment (PT), followed by a decrease to undetectable levels 12 months after treatment. To further explore the mechanisms of these changes in frequency in parasite-specific memory T cells, we 1) analyzed the expression of two hallmarks of bona fide memory T cells on T. cruzi-specific T cells, the homeostatic receptor CD122 (IL2R_/IL15R_) and the lymphoid homing molecule CCR7, to determine if the increase in parasite-specific T cells early after treatment corresponds to long-lived T cells and 2) used in vitro culture to attempt to expand the population of remaining T. cruzi -specific T cells possibly present at 12 months PT. The phenotypic analysis of T. cruzi-specific memory T cells at 2-6 months PT showed that in all individuals evaluated, T. cruzi-specific IFN-g-producing T cells did not differ from those observed prior to treatment, with low expression of CD122 and CCR7. Likewise, when parasite-specific T cells with the capacity to simultaneously produce IFN-g and IL-2 were detected, these cells were also negative for the markers tested. In individuals who lacked T. cruzi-specific T cell responses responses at 12 months PT, a round of in vitro stimulation failed to expand the population of T. cruzi responsive cells. However, samples from these same subjects taken prior to treatment displayed a10-20 fold expansion of T. cruzi-specific IFN-g-secreting T cells. These data demonstrate that treatment with BZ during the chronic phase may induce a transient increase of effector memory T cells specific for T. cruzi with phenotypic features of short-lived T cells. These changes may be useful surrogate markers for assessing treatment efficacy.