Lsp1-/- DENDRITIC CELLS INDUCE POOR PROLIFERATION OF CD4+ T LYMPHOCYTES

DHO ND, PASCUAL MM, CRESPO MI, MARÍN C, PISTORESI MC, MALETTO B, MORÓN G

Congreso; LXVII REUNIÓN SAI; 2019

85. Lsp1-/- DENDRITIC CELLS INDUCE POOR PROLIFERATION OF CD4+ T LYMPHOCYTESDho ND, Pascual MM, Crespo MI, Marín C, Pistoresi MC, Maletto B, Morón G.CIBICI, CONICET-UNC.Leukocyte-specific protein 1 (LSP1) is a 52 kDa cytoplasmic F-actin binding phosphoproteinexpressed in all human and murine leukocytes and endothelial cells. LSP1 is an importantregulator of actin cytoskeleton remodeling. We have previously shown that Lsp1-/- mice have animpaired CTL response after antigen exposure, with Lsp1-/- dendritic cells (DCs) failing toinduce a strong CTL response in vivo.In order to study the role of LSP1 in DCs to promote a CD4+ T cell-mediated response, we firstevaluated the capacity of Lsp1-/- DCs to activate CD4+ T cells. In vitro, bone marrow dendriticcells (BMDCs) were derived from Lsp1-/- mice with Flt3-L. BMDCs were pulsed with soluble orparticulated Ovalbumin (OVAw or OVAb, respectively), then stimulated with CpG-ODN 1826and finally cocultured with CD4+ T cells purified from OT-II mice, previously stained with e-Fluor 670 proliferation dye. Three days later, a significantly lower percentage of proliferatingcells was observed with Lsp1-/- BMDCs incubated with OVAw (p< 0.0001) and OVAb (p<0.0001), and CD25 expression with Lsp1-/- BMDCs incubated with OVAb (p< 0.005) compared toLsp1+/+ BMDCs. In vivo, CD4+ T cells from OT-II mice were equally stained and injected intoLsp1-/- mice. Twenty-four hours later, mice were immunized with OVAw+CpG-ODN. Three dayslater, we observed a significantly lower frequency of proliferating CD4+ T cell in draining lymphnodes (p< 0.05) in Lsp1-/- mice compared to Lsp1+/+ mice.These results suggest that LSP1 deficiency affects CD4+ T cell activation, which could impairinduction of effector responses in mice.