IL-17A reverts the reduction in CD8+ T cell response generated by anti-CD20 treatment

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

Mar del Plata

Congreso; LXVI Reunión Anual de la Sociedad Argentina de Inmunología; 2018

Sociedad Argentina de Inmunología

Anti-CD20 therapy, that depletes B cells, is widely usedto treat autoimmunity and lymphomas. B cells can regulateT cell responses because they have antibody independentfunctions, such as antigen presentation andcytokine secretion. To evaluate the effect of anti-CD20treatment on CD8+T cell response we used the experimentalmodel of Trypanosoma cruzi infection, sinceCD8+T cells are essential for infection control.For that, anti-CD20 mAb was injected eight days beforeinfection with 5000 trypomastigotes, to deplete B cellsand CD8+T cell response was analyzed at different dayspost infection (dpi). Infected control mice were injectedwith an isotype antibody.At 20 dpi, B-cell depleted mice (BcD) exhibited higherparasitism (determined by parasite DNA quantificationby RT-PCR) in the spleen, liver and heart than controls(p<0,001). Interestingly, an early contraction of totaland T. cruzi-specific CD8+T cell response, measuredby FACS using tetramers, was observed in BcD mice.Infected BcD mice had significant lower frequency andnumber of splenic CD8+T cells (p<0,05), decreasedCD8+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-celllysis in comparison to controls. CD8+T cells from BcDmice also exhibited reduced cytokine production. Whenanti-CD20 was injected after 12 dpi, CD8+T cells exhibitedthe same characteristics than those present in miceinjected before infection, suggesting that B cells did notinfluence CD8+T cell response through antigen presentation.Immunofluorescence studies showed that T cellswere in a narrow zone of contact with extrafollicularIL-17A-producing plasmablasts. Moreover, the frequencyof splenic IL-17A-producing cells from infected BcD micewas strongly reduced. IL-17A administration to infectedanti-CD20 treated mice rescued the overall CD8+T cellresponse. The results indicate that IL-17A production byB cells or other IL-17A producing cells are key to sustainCD8+T cell response.