LSP1 DEFICIENT DENDRITIC CELLS ARE RESPONSIBLE FOR GENERATING AN INADEQUATE CYTOTOXIC IMMUNE RESPONSE

MERCEDES PASCUAL; BELKYS MALETTO; GABRIEL MORÓN; RACHEL PAOLA ACLAND STRACK; MARÍA CRISTINA PISTORESI

Mar del Plata

Congreso; LXIV Reunión Científica de la Sociedad Argentina de Inmunología (SAI)/SAIC/SAFE; 2016

SAI/SAFE/SAIC

Background: Leukocyte-specific protein 1 (LSP1), is a 52-kDa cytoplasmic F-actin binding phosphoprotein expressed in all human and murine leukocytes as well as in endothelial cells. LSP1 is an important regulator of actin cytoskeleton remodeling, modulating leukocytes motility. We previously showed that Lsp1-/- mice have an impaired CTL response after antigen exposure. We have also reported that Lsp1-/- dendritic cells (DCs) fail to induce a strong CTL response in vivo, with minimal alterations in T cell compartment. In order to study the role of LSP1 in the ability of DCs to induce immunity, we phenotypically and functionally characterized Lsp1-/- DCs.Methods: Murine bone marrow DCs (BMDCs) from Lsp1-/- and wild-type mice (B6 background) were differentiated with Flt3L during 10 days and then stimulated for 18h with CpG-ODN. After stimulus, phenotypic maturation was determined by flow cytometry, and MHC I-restricted antigen presentation, was analyzed by incubating DCs with latex beads conjugated to OVA and further incubation with the H2-Kb-restricted OVA257-264-specific CD8+ T cell hybridoma (B3Z).Results: BMDCs differentiate at similar rates from Lsp1-/- and wt mice, reaching in both cases 85-90% of CD11c+ cells. After CpG-ODN stimulus, the frequency of CD8+ DCs and pDCs equally raise up to 20% in Lsp1-/- and wt BMDCs. Lsp1-/- BMDCs show similar expression of CD40, CD86 and PDL2 but lower of I-Ab than wt BMDCs (p