CHARACTERIZATION OF FOXP3+ REGULATORY T CELL RESPONSES DURING EXPERIMENTAL TRYPANOSOMA CRUZI INFECTION

ARAUJO FURLAN, CINTIA; TOSELLO BOARI, JIMENA; CANALE, FERNANDO; RAMELLO, MARIA CECILIA; GRUPPI, ADRIANA ; MONTES, CAROLINA LUCIA; ACOSTA RODRIGUEZ E V

Los Cocos

Jornada; LXI Reunión Anual de la sociedad argentina de Inmunología .; 2013

CHARACTERIZATION OF FOXP3+ REGULATORY T CELL RESPONSES DURING EXPERIMENTAL TRYPANOSOMA CRUZI INFECTION Araujo Furlan, Cintia Liliana ; Tosello Boari, Jimena ; Canale, Fernando ; Ramello, María Cecilia ; Gruppi, Adriana ; Montes, Carolina ; Acosta Rodriguez, Eva ; CIBICI - CONICET, Facultad de Ciencias Químicas, Universidad Nacional de Córdoba   CD4+ T cells expressing CD25 and Foxp3 (Tregs) regulate immune responses and, consequently, influence the pathogenesis of infectious diseases. Regulatory response during T. cruzi infection has been poorly characterized and Treg roles remain controversial after few studies based on Treg depletion and GITR and CTLA-4 blockade. Our aim is to characterize the magnitude and quality to further elucidate the role of Treg response during experimental T. cruzi infection.  For this, Foxp3-GFP mice were infected with 5000 T. cruzi tripomastigotes and Tregs (GFP+CD4+CD25+ cells) were enumerated and characterized at different days (d) postinfection (pi) by flow cytometry. The absolute numbers of Tregs remained constant or were slightly increased in all the organs studied while the numbers of effector subsets regulated by Tregs (i.e. CD4 and CD8 T cells and B cells) were greatly augmented in spleen, lymph nodes and liver but not in thymus. Thus, the ratio of Tregs to effector cells was significantly diminished in the periphery from d10 until d60pi (early chronic phase, last day of study) (spleen: d0pi 0.134±0.012 vs d20pi 0.056±0.008, p<0.005; and d60pi 0.081±0.008, p<0.01). In contrast, Tregs were overrepresented in thymus. Phenotypic profiling of Tregs showed that some characteristics such as CD44hiCD62LlowCD127lowCD73hi were conserved during infection whereas other markers as CD103 and CTLA-4 were significantly upregulated. Of note, a fraction of Tregs expressed CXCR3 and produced IFNg upon infection showing plastic attributes. Analysis of putative markers of thymic origin at d15pi showed that the percentage of Tregs expressing Helios remained unchanged but Neuropilin-1 expression was significantly downregulated. Our results suggest that Tregs are activated during T. cruzi infection but the number of Tregs is overwhelmed by the number of effector cells. This may be associated with the tissue damage observed. Our data provide a rationale for enhancing Treg response to prevent immunopathology.