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

Erlanger

Congreso; 47th Annual Meeting of the German Society for Immunology. 12 al 15 de Septiembre de 2017. Erlanger, Alemania.; 2017

German Society for immunology

Introduction and objectives: CD8+ T cells are key elements in the defense against T.cruzi infection. Then, the factors that promote the generation and maintenance of CD8+T cell responses need to be studied in deep. B cells have been reported as critical for optimal CD8+T cell responses in cancer and infections. Based on this, the aim of our work was to analyze the role of B cell 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 were intraperitoneally injected with anti-CD20, to deplete B cells, or with control antibody. Eight days after treatment, mice were infected with 5000 trypomastigotes of Tulahuén strain. Tissue parasitic DNA quantification was assessed by real time PCR and T. cruzi-specific CD8+ T cell response was measured by FACS using tetramers containing the parasite peptide TSKB20. Phenotype and function of CD8+ T cells were also analyzed by FACS. In vivo CD8+ T cell function was studied by FACS after transfer of unpulsed or Tksb20-pulsed splenic cells stained with different dyes. The frequency of cytokine-producing cells was analyzed in splenocytes 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. At 20 day post infection (dpi), infected BcD mice exhibit a significant lower frequency and number of Tskb20+CD8+T cells in blood, spleen and liver (p=0.01) and lower frequency of effector memory CD8+T cells and short-lived effectors cells (KLRG-1+CD127-) and a significant higher frequency of naïve CD8+T cells, than infected controls.Furthermore, total and parasite-specific CD8+T cells from infected BcD mice exhibited less grade of activation and higher levels of inhibitory receptors, and showed reduced cytotoxicity, IFNg and TNF production. Interestingly, infected mice in which B cells depletion was performed at 14 dpi also exhibit lower percentage of parasite-specific CD8+T cells, suggesting that B cells are not 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 we observed a strong reduction in total cells producing these cytokines in BcD mice.