Follicular CD8+ T cells in Trypanosoma cruzi infection: helpers or killers depending on the target B cell population.

Follicular cytotoxic T (Tfc) cells are a distinct subset of CD8 ⁺ T cells predominantly localized in B cell follicles and their surrounding areas. These cells play important roles in supporting B cell responses and controlling pathogens through the elimination of infected cells. Although their involvement in immune-mediated diseases and tumors is well-documented, their role in parasitic infections remains largely unexplored. Through phenotypic and transcriptomic analysis, we identified a specialized Tfc population that transiently emerges during the acute phase of Trypanosoma cruzi infection. Tfc cells in this context were composed mainly of effector cells, peaked concurrently with plasmablasts, and preceded the germinal center response. They exhibited high expression of proteins associated with B cell help, inflammatory chemokine receptors, and transcription factors linked to effector functions. In vitro assays revealed that Tfc cells display dual functionality: they promote antibody secretion by naïve and stimuli-activated B cells, and they also exert cytotoxic activity against plasmablasts, the antibody-producing cells present during the acute phase, through Fas/FasL interactions. Altogether, these findings suggest that Tfc cells may contribute to the regulation of early antibody responses during T. cruzi infection by combining helper and cytotoxic functions.