Absence of B cells results in a defective CD8+T cell response in Trypanosoma cruzi infection

ACOSTA RODRÍGUEZ, EVA VIRGINIA; ARAUJO FURLÁN, CINTIA; FIOCCA VERNENGO, FACUNDO; MONTES, CAROLINA LUCÍA; TOSELLO BOARI, JIMENA; GRUPPI, ADRIANA; GOROSITO SERRÁN, MELISA; BECCARIA, CRISTIAN GABRIEL

Erlangen

Congreso; 47th Annual Meeting of the German Society for Immunology; 2017

German Society for Immunology

Introduction and objectives: CD8+ T cells are key elements in the defense against T.cruzi infection. Then, thefactors that promote the generation and maintenance of CD8+T cell responses need to be studied in deep. Bcells have been reported as critical for optimal CD8+T cell responses in cancer and infections. Based on this, theaim of our work was to analyze the role of B cells on CD8+T cell response during T. cruzi infection.Methods: To assess B-cell function on CD8+ T cell response in T. cruzi infection, C57BL/6 mice wereintraperitoneally injected with anti-CD20, to deplete B cells, or with control antibody. Eight days aftertreatment, mice were infected with 5000 trypomastigotes of T. cruzi Tulahuén strain. Tissue parasitic DNAquantification was assessed by real time PCR and T. cruzi-specific CD8+ T cell response was measured by FACSusing tetramers containing the parasite peptide TSKB20. Phenotype and function of CD8+ T cells were alsoanalyzed by FACS. In vivo CD8+ T cell function was also studied by FACS after transfer of unpulsed or Tksb20-pulsed splenic cells stained with different dyes. The frequency of cytokine-producing cells was analyzed insplenocytes from both infected groups of mice cultured with Tskb20, PMA+Io or medium alone.Results: We found B cell-depleted (BcD) mice infected with T. cruzi had higher parasite load than controls. At20 day post infection (dpi), infected BcD mice exhibit a significant lower frequency and number ofTskb20+CD8+T cells in blood, spleen and liver (p=0.01) and lower frequency of memory (CD62L-CD44+) andshort-lived effectors (CD44+KLRG-1+CD127-) CD8+ T cells; and a significant higher frequency of naïve(CD62L+CD44-) CD8+T cells, than infected controls. Furthermore, total and parasite-specific CD8+T cells frominfected BcD mice exhibited less grade of activation and higher levels of inhibitory receptors, and showedreduced cytotoxicity, IFN and TNF production. Interestingly, infected mice in which B cell depletion wasperformed at 14 dpi also exhibit lower percentage of parasite-specific CD8+T cells, suggesting that B cells arenot necessary for CD8+ T cell priming.Conclusion: The results identified that B cells are key for T. cruzi specific CD8+ T cell maintenance and function.Some of these effects could be mediated by cytokines produced by B cells such as IL-17 and IL-6 since weobserved a strong reduction in total splenic cells producing these cytokines in BcD mice.