Vaccination strategy based on LPS-activated dendritic cells induces CD8+ T cell response capable of conferring partial protection against Trypanosoma cruzi infection.

BISCARI, LUCÍA; ALLOATTI, ANDRÉS

Congreso; LXX Reunión Anual de la Sociedad Argentina De Inmunología (SAI) & 3er Congreso Franco-Argentino De Inmunología (FAIC); 2022

Sociedad Argentina de Inmunología

CD8 + T cells are key components of the immune response against Trypanosoma cruzi, and in this sense, the design of vaccines that induce such responses may be promising.In this work, a vaccination strategy based on mouse bone marrow-derived dendritic cells ?BMDCs?, incubated with a parasitic peptide TsKb20 ? derived from the transialidase protein of T. cruzi ? and activated with LPS, was designed in order to induce a TsKb20-specific CD8 + T cell response. The experimental scheme was as follows: C57BL/6 mice were immunized intravenously with 50,000 TsKb20-loaded BMDCs, followed by a boost two weeks later. One group of animals was immunized with BMDCs not activated and not loaded with peptide (negative control). Fifteen days after the boost, cell suspensions derived from lymph nodes were cultured for 15 h with 50 uM TsKb20. The specific CD8 + T cell response was measured by flow cytometry evaluating CD25 + and CD69 + activation markers in the CD8 + T cell population. Through non-parametric Mann-Whitney test, it was found that the TsKb20-specific CD8 + T cell response in animals immunized with peptide-loaded BMDCs was significantly higher than in negative control animals. The same results were obtained by measuring IFN-γproduction by ELISPOT after restimulation with the peptide, or by staining with specific tetramers. Another pool of animals was immunized and then challenged with 2000 T. cruzi trypomastigotes. Female mice, but not male mice, showed lower 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 cell responses, although these appear to be protective only in female mice.