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

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

Congreso; Reunion 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 cellresponse need to be studied in deep. The aim of our work was toanalyze the role of B cells on CD8+T cell response during T.cruziinfection.For this, 8 days before intraperitoneal (ip) infection with 5000 trypomastigotesof T.cruzi Tulahuén strain, C57BL/6 mice were ip injectedwith anti-CD20 (BcD mice), to deplete B cells, or with controlisotype. At 20 days post infection (dpi), tissue parasitic DNA quantificationwas assessed by real time PCR and T.cruzi-specific CD8+Tcell response was measured by FACS using tetramers loaded withthe parasite immunodominant peptide Tskb20. Phenotype and functionof 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 numberof Tskb20+CD8+T cells in blood, spleen and liver (p=0.01), lowerfrequencies of short-lived (p=0,03) and memory (p=0,02) effectorcells, and a significant higher frequency of naïve CD8+T cells, thaninfected controls. Total and T.cruzi-specific CD8+T cells from infectedBcD mice exhibited a lesser extent of activation and proliferationbut higher levels of inhibitory receptors. In agreement, CD8+T cellsfrom infected BcD mice presented reduced cytotoxicity, degranulation,IFNɣ and TNF production (p=0,02). When infected mice with asettled down specific-CD8+T cell response (12dpi) were depletedfrom B cells, interestingly, they exhibited the same characteristicsthan those depleted before infection. Injection of recombinant IL-17rescued the frequency, phenotype and function of CD8+T cells generatedin B cell absence.Results indicate that B cells are key for T. cruzi specific CD8+T cellmaintenance and function, but are not necessary for their induction.Considering B cells produce IL-17 in T. cruzi infection probably itsfunction on CD8+ T cells depends on IL-17.