Experimental Trypanosoma cruzi infection induces changes in the proportion of CD4+FoxP3+ thymic and peripheral cells.

RODRIGO FERNANDEZ BUSSY1, SILVINA VILLAR1, ROMINA MANARIN1, GAELLE MARTIN2, SILVIA REVELLI1, ELIANE PIAGGIO2, JOSÉ COHEN2, OSCAR BOTTASSO1, ANA ROSA PÉREZ1. ; VILLAR, SILVINA RAQUEL

Rosario

Congreso; XXXI Congreso Nacional de cardiología; 2013

Federacion Argentina de Cardiología

Regulatory CD4+FoxP3+ T cells (Treg) develop in the thymus and control inflammatory response during autoimmune and infectiousprocesses. This populationplaysantagonisticroles during parasitic infections, promoting the survival of either the host or the microorganism. Since infection with T. cruzi (Tc) affects primary and secondary lymphoid organs; i.e., the thymus where Treg cells originate, we investigated the phenotype of Tregcellsin two mouse strains with different degrees of susceptibility to acute T, cruzi infection (C57BL/6 strain -B6- has 100% mortality, whereas 30% of BALB/ c surviveand evolve to the chronic phase). Data from flow cytometry studies in thymus (median/range 3-6 mice/group) showed a baseline rate ofTregslightly larger in BALB/c mice than in B6 [(%), B6-Co 4.1/(5.2-4.5) BALB/c-Co6.4/(6.9-6.1) p <0.05]. In both strains, infection resulted in a progressive enrichment of CD4+FoxP3+ [day 17pi (%) B6-Tc 4.5/(8.0-3.2), BALB/c-Tc 10.6/(11.7-7,1), p<0.05], although severethymusatrophycauseda significant reduction in absolute numbers. Relative expression of FoxP3mRNA(real-time PCR) decreased in B6,while increasedinBALB/c [day 14pi (2-ΔΔCT) B6-Tc 0.5,BALB/c-Tc 4.4 (n=4/group)]. FoxP3+ cells localization determined by confocalmicroscopy was mostlymedullary.In blood, spleen and subcutaneous lymph nodes it was found a strong expansion ofTregpopulationin absolute numbers, paralleled by a marked decrease in their frequency [day 21pi, spleen (%), B6​​-Co 12.7/(13.0-12.0) B6-Tc 4.7/(6.1-2.9) BALB/c-Co 18.0/(19.4-16.7), BALB/c-Tc: 5.6/(6.0-2,9), Covs Tc p<0.05 inboth cases] caused by the expansion of the effectorT cell population(Teff, CD4+FoxP3-) [RatioTeff/TregB6-Tc 20.0/(33.2-15.4) BALB/c-Tc: 16.0/(33.0-15.6)]. CD25+ T cell depletion with PC61 before infection did not prevent the expansion ofCD4+FoxP3+cellsafter7 dayspi in both strains of mice. Since interleukin-2 (IL-2) in low doses promotes T reg cell development, mice were treated with rmIL-2 (50.000 UI) during the first 5 or 10 days of infection. Treatment failed to increasethe expansion ofT regs, but attenuated parasitemia.Tc infection accompanying disturbances of Tregs in the thymic compartment, together with the marked diminutionin the proportion of Tregin secondary lymph organs, may contribute to the pathogenesis of chronicdisease. Further studies will be carried out to assess whether differences in acute disease susceptibility are related with functional variations of Tregs.