IL-17A REVERTS THE REDUCTION IN CD8+ T CELL RESPONSE GENERATED BY ANTI-CD20 TREATMENT.

FIOCCA VERNENGO, FACUNDO; BECCARIA, CRISTIAN GABRIEL; ALMADA, LAURA; ARAUJO FURLAN, CINTIA LILIANA; TOSELLO BOARI, JIMENA; GOROSITO SERRÁN, MELISA; GAZZONI, YAMILA; MONTES, CAROLINA LUCÍA; ACOSTA RODRIGUEZ, EVA V.; GRUPPI, ADRIANA

Mar del Plata

Congreso; SAIC SAI SAFIS 2018; 2018

Sociedad Argentina de Inmunología

Anti-CD20 therapy, that depletes B cells, is widely used to treat autoimmunity and lymphomas. B cells can regulate T cell responses because they have antibody independent functions, such as antigen presentation and cytokine secretion. To evaluate the effect of anti-CD20 treatment on CD8+T cell response we used the experimental model of Trypanosoma cruzi infection, since CD8+T cells are essential for infection control. For that, anti-CD20 mAb was injected eight days before infection with 5000 trypomastigotes, to deplete B cells and CD8+T cell response was analyzed at different days post infection (dpi). Infected control mice were injected with an isotype antibody. At 20 dpi, B-cell depleted mice (BcD) exhibited higher parasitism (determined by parasite DNA quantification by RT-PCR) in the spleen, liver and heart than controls(p<0,001). Interestingly, an early contraction of total and T cruzi-specific CD8+T cell response, measured by FACS using tetramers, was observed in BcD mice. Infected BcD mice had significant lower frequency and number of splenic CD8+T cells (p<0,05), decreased CD8+T cell proliferation (p<0,05), higher levels of apoptosis (p<0,01) and expression of inhibitory receptors (p<0,05) on CD8+T cells, and lower in vivo infected-cell lysis in comparison to controls. CD8+T cells from BcD mice also exhibited reduced cytokine production. When anti-CD20 was injected after 12 dpi, CD8+T cells exhibited the same characteristics than those present in mice injected before infection, suggesting that B cells did not influence CD8+T cell response through antigen presentation. Immunofluorescence studies showed that T cells were in a narrow zone of contact with extrafollicular IL-17A-producing plasmablasts. Moreover, the frequency of splenic IL-17A-producing cells from infected BcD mice was strongly reduced. IL-17A administration to infected anti-CD20 treated mice rescued the overall CD8+T cell response. The results indicate that IL-17A production by B cells or other IL-17A producing cells are key to sustain CD8+T cell response.