B cells sustein Trypanosoma cruzi specific CD8+ T cell response via IL-17

F FIOCCA VERNENGO; CG BECCARIA; L ALMADA; CL ARAUJO FURLAN; J TOSELLO BOARI; CL MONTES; EV ACOSTA RODRIGUEZ; A GRUPPI

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

CD8+T cells are key in the defense against T.cruzi infection. Then, factors that promote the generation and maintenance of CD8+T cell response need to be studied in deep. The aim of our work was to analyze the role of B cells on CD8+T cell response during T.cruzi infection. For this, 8 days before intraperitoneal (ip) infection with 5000 trypomastigotes of T.cruzi Tulahuén strain, C57BL/6 mice were ip injected with anti-CD20 (BcD mice), to deplete B cells, or with control isotype. At 20 days post infection (dpi), tissue parasitic DNA quantification was assessed by real time PCR and T.cruzi-specific CD8+T cell response was measured by FACS using tetramers loaded with the parasite immunodominant peptide Tskb20. Phenotype and function of CD8+ T cells were also analyzed by FACS. Infected BcD mice exhibited higher parasitism than controls. Further, infected BcD mice had a significant lower frequency and number of Tskb20+CD8+T cells in blood, spleen and liver (p=0.01), lower frequencies of short-lived (p=0,03) and memory (p=0,02) effector cells, and a significant higher frequency of naïve CD8+T cells, than infected controls. Total and T.cruzi-specific CD8+T cells from infected BcD mice exhibited a lesser extent of activation and proliferation but higher levels of inhibitory receptors. In agreement, CD8+T cells from infected BcD mice presented reduced cytotoxicity, degranulation, IFNɣ and TNF production (p=0,02). When infected mice with a settled down specific-CD8+T cell response (12dpi) were depleted from B cells, interestingly, they exhibited the same characteristics than those depleted before infection. Injection of recombinant IL-17 rescued the frequency, phenotype and function of CD8+T cells generated in B cell absence. Results indicate that B cells are key for T. cruzi specific CD8+T cell maintenance and function, but are not necessary for their induction. Considering B cells produce IL-17 in T. cruzi infection probably its function on CD8+ T cells depends on IL-17.