VACCINATION STRATEGY BASED ON LPS-ACTIVATED DENDRITIC CELLS INDUCES CD8+ T CELL RESPONSE CAPABLE OF CONFERRING PARTIAL PROTECTION AGAINST TRYPANOSOMA CRUZI INFECTION

LUCÍA BISCARI; CINTIA D. KAUFMAN; CECILIA FARRÉ; VICTORIA HUHN; MARÍA FLORENCIA PACINI; CAMILA BULFONI BALBI; KARINA A. GÓMEZ; ANA R. PÉREZ; ANDRÉS ALLOATTI

Mar del Plata

Congreso; LXX REUNIÓN ANUAL DE LA SOCIEDAD ARGENTINA DE INMUNOLOGÍA (SAI) & 3ER CONGRESO FRANCO-ARGENTINO DE INMUNOLOGÍA (FAIC); 2022

Sociedad Argentina de Inmunologia

CD8+ T cells are key components of the immune response againstTrypanosoma cruzi, and hence, the design of vaccines able to induce such responses is a promising strategy. In this work, a vaccination strategy based on mouse bone marrow-derived dendriticcells (BMDCs), incubated with a parasitic epitope named TsKb20 –derived from the transialidase protein of T. cruzi – and activated withLPS, was designed in order to induce a TsKb20-specific CD8+ T cellresponse. The experimental scheme was as follows: C57BL/6 micewere immunized intravenously with 50,000 TsKb20-loaded BMDCsactivated with LPS, followed by a boost two weeks later. One groupof animals was immunized with LPS-activated BMDCs not loadedwith peptide (negative control). Fifteen days after the boost, cell suspensions derived from lymph nodes were cultured for 15 h with 50μM TsKb20. The specific CD8+ T cell response was measured byflow cytometry evaluating CD25+ and CD69+ activation markers inthe CD8+ T cell population. Through non-parametric Mann-Whitneytest, it was found that the TsKb20- specific CD8+ T cell response inmice immunized with peptide-loaded BMDCs was significantly higher than in negative control animals. The same results were obtainedby measuring IFN-γ production by ELISPOT after restimulation withthe peptide, or by staining with specific tetramers. Subsequently, another pool of animals was immunized and then challenged with 2000T. cruzi trypomastigotes. Female mice, but not male mice, showedlower parasitemia and increased survival compared to negative control animals. These results suggest that the adoptive transfer of BMDCs could be used as a strategy to induce anti-T. cruzi CD8+ T cellresponses, although these appear to be protective only in femalemice possibly due to sexual dimorphism in the immune responsegenerated upon infection with T. cruzi