DC TARGETING AS A STRATEGY FOR INDUCING TRYPANOSOMA CRUZI SPECIFIC CD8+ T CELL RESPONSES

BISCARI, LUCÍA; KHOUILI, SOFÍA C.; COOK, EMMA C.; KAUFMAN, CINTIA D.; FARRE, CECILIA; DERIO, MARISA; IBORRA, SALVADOR; PEREZ, ANA ROSA; SANCHO, DAVID; ALLOATTI, ANDRES

San Luis

Jornada; LXXI Reunión Científica Anual de la Sociedad Argentina de Inmunología SAI; 2023

Universidad Nacional de San Luis-San Luis

In the immune response against Trypanosoma cruzi, CD8+ T cells are crucial forparasite control and survival during the acute phase of infection. We havepreviously determined that cross-presentation of antigens (XP) is a relevantmechanism involved in the induction of such responses orchestrated by dendriticcells (DCs). Within the subpopulations of DCs, conventional type 1 DCs (cDC1s),which express the endocytic receptor Clec9A, perform XP most efficiently. Sincethere are currently no vaccines to prevent or treat Chagas disease, in this workwe evaluated a prophylactic vaccination strategy based on antigen targeting ofcDC1s in C57BL/6 mice with the aim of inducing CD8+ T cell responses. Chemicalconjugates of the TsKb20 peptide – immunodominant epitope derived from the T.cruzi trans-sialidase protein – with anti-Clec9A monoclonal antibody or anantibody without receptor affinity (isotype control) were obtained to immunizemice intravenously together with poly (I:C) as adjuvant. Non-immunized animals,animals immunized with non-targeted TsKb20 and poly (I:C) or animals thatreceived only the adjuvant were used as additional controls. One week later, theanimals were sacrificed and splenocytes were obtained to assess the specificeffector response of CD8+ T cells by staining with tetramers, analysis of CD25and CD69 activation markers, and Th1-type cytokine production after in vitrorestimulation with TsKb20 peptide. Flow cytometric analysis of splenocytesderived from mice that had received TsKb20-conjugated anti-Clec9A showed apopulation of tetramer-positive CD8+ T cells and increased expression of CD25and CD69 markers in response to incubation with TsKb20 peptide in contrast tothe rest of the groups (overall p