GERMINAL CENTER REACTION IN Trypanosoma cruzi INFECTION: CHARACTERIZATION OF FOLLICULAR CYTOTOXIC CD8+T CELLS

GAZZONI YAMILA; ALMADA LAURA; ABRATE CAROLINA; MONTES CAROLINA LUCÍA; ACOSTA RODRÍGUEZ EVA V.; GRUPPI ADRIANA

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2020; 2020

Germinal Centers (GCs) are specialized structures generated within the B cell follicles in response to T cell-dependent antigens in which B cells differentiate into antibody-secreting cells and memory B cells. Follicular helper T cells (Tfh) are crucial for GCs formation and antibody-affinity maturation. Other GCs-protagonists are follicular cytotoxic CD8+T cells (Tfc), who share gene signatures with Tfh cells but their function is not well established. In some models, Tfc contribute to eliminate infected cells inside the follicle.Our aim was to study different protagonists of GC reaction and plasmablasts(PB) response along T. cruzi infection. For that, C57BL/6 mice were intraperitoneally infected with 5.000 trypomastigotes of T. cruzi (Tulahuén strain) and the frequency and number of Tfh, Tfc and PB were evaluated by flow cytometry at different days post infection(dpi) in the spleen. Mice injected with PBS were used as controls.We observed that the peak of the Tfh(CD4+CXCR5+PD-1+ICOS+), Tfc(CD8+CXCR5+PD-1+ICOS+) and PB(B220loCD138+) response was at 18dpi.These responses preceded GC-B cell response (B220+FAS+GL-7+Bcl-6+)which peaked at 28 dpi. Tfc had a higher expression of Bcl-6 and Tcf-1 than non-Tfc CD8+ T cells(p<0,05). Near 25% of Tfc, but only 3% of non-Tfc, were specific for the immunodominant T. cruzi TSKB20 peptide. Tfc were CD107a+ and IFN-y, TNF-a, Granzyme B and Perforin-producing cells. By immunofluorescence of spleen sections, at 15 dpi, we detected CD8+T cells inside and around B cells follicles and spatially opposed to follicular dendritic cells; at 23dpi and 28dpi, all CD8+T cells were outside the follicles and some of them in close contact with PB.To sum up, we observed an activated CD8+T cells subset whose peak of the response was prior to CG, expressed Tfh-related molecules and were observed in close contact with B cells subsets. Tfc could be influencing humoral response, controlling infection more efficiently, or regulating some population of CG.