DYNAMIC OF FOLLICULAR CYTOTOXIC CD8+T CELL RESPONSE IN TRYPANOSOMA CRUZI INFECTION

GAZZONI, YAMILA; ALMADA, LAURA; MONTES, CAROLINA LUCIA; ACOSTA RODRÍGUEZ, EVA V.; GRUPPI, ADRIANA

Congreso; REUNIÓN DE SOCIEDADES DE BIOCIENCIAS 2021; 2021

Germinal Centers (GCs) are specialized structures generated within B cell follicles (FO) in response to T cell-dependent antigens. Follicular helper T cells (Tfh) are crucial for GC formation and antibody-affinity maturation. Other GCs-protagonists are follicular cytotoxic CD8+T cells (Tfc), who share gene signatures with Tfh cells and, in some models, contribute to eliminate infected cells inside the FO.Our aim was to study protagonists of GC response in T. cruzi infection and to characterize Tfc cells. C57BL/6 mice were intraperitoneally injected with 5.000 trypomastigotes of T. cruzi (Tulahuén strain) or PBS (control group). Tfc, GC B cells, and plasmablasts (PB) were evaluated by FACS and immunofluorescence (IF) staining at different days post infection (dpi) in the spleen. The peaks of the Tfc (CD8+CXCR5+PD-1+) and PB (B220lowCD138+) response were at 18dpi and decreased at 23 dpi. These populations preceded GC-B cell(B220+FAS+GL-7+) response which peaked at 28 dpi. About 80% of Tfc were CD44+CD62-Llow and had a higher expression of Bcl-6, TCF-1, Lag-3, CD40-L and CXCR3 than non-Tfc CD8+T cells (p<0,05). Near 15% of Tfc and 6% of non-Tfc, were specific for the immunodominant T. cruzi TSKB20 peptide. After in vitro stimulation with PMA/Io or TSKB20, Tfc expressed high levels of CD107a+,IFN-y, TNF-a, Granzyme B and Perforin. By IF we detected CD8+T cells inside of FO at 18 dpi; while at 23dpi and 28dpi all CD8+ T cells were outside. Additionally, we observed that IL-15 and IL-21 increased Tfc survival in vitro.To sum up, we observed an activated, effector and temporal CD8+T cell subset whose response was prior to GC, expressed Tfh-related molecules and were in contact with B cells. Co-culture experiments are needed to dilucidate the relationship between Tfc and B cell in T. cruzi infection. Tfc could influence antibody response by interacting with PB or GC; or could control the infection since parasite-infected cells were observed inside B cell FO.