B cell depletion compromises CD8+ T cell response in murine T cruzi infection

F FIOCCA VERNENGO; CG BECCARIA; C ARAUJO FURLAN; J TOSELLO BOARI; M GOROSITO SERRÁN; C MONTES; E ACOSTA RODRIGUEZ; A GRUPPI

Melbourne

Congreso; International Congress of Immunology (ICI 2016); 2016

Considering CD8+T cells play a major role in T. cruzi protective immunity, the signals that promote the generation and maintenance of CD8+T cell responses needs to be identified. Many reports highlight the role of B cells in promoting cellular immunity; however, if B cells affect CD8 responses remain uncharacterized. To assess B-cell function in promoting CD8 responses in Chagasdisease, C57BL/6 mice were intraperitoneally injected with anti-CD20, to deplete B cells, or with control antibodies. Eight days after treatment, mice were infected with 5000 trypomastigotes. Flow cytometric analysis using tetramer staining revealed that at day 14 post infection, depleted mice had a lower frequency of parasitespecific CD8+T cells in spleen, blood and liver compared to control mice (p=0,0003, 0,0353 and 0,0447 respectively). Interestingly, B-celldeficient mice showed higher percentages of naïve CD8+T cells (CD44-CD62L+) and lower frequency of effector memory CD8+T cells (CD44+CD62L-). CD8+T cells from B-cell depleted mice presented a Memory Precursor Effectors Cells phenotype unlike CD8+T cells from B-cell sufficient mice who exhibit a Short Lived Effectors Cells phenotype. Also, we found that depleted mice had lowerfrequencies of IFN-γ- or TNF-producing CD8+T cells and displayed lower apoptosis and proliferation rate. Unexpectedly CD8+T cells from B-cell depleted mice overexpressed molecules associated to activation/migration than control mice. These results identify functional defects in CD8+T cells generated in B cell-depleted mice, highlighting B cell influence on CD8+T cell response. Furthermore, our study urges caution during B-cell depletion therapies due to its possible side effects on the immunity against infections.