cxcl10 is critical for the generation of protective cd8 t cell response induced by antigen pulsed cpg-odn activated dendritic cellscxcl10至关重要的一代保护性cd8 t细胞反应抗原引起的脉冲cpg-odn激活树突状细胞.pdfVIP

CXCL10 Is Critical for the Generation of Protective CD8 T Cell Response Induced by Antigen Pulsed CpG-ODN Activated Dendritic Cells Saikat Majumder, Surajit Bhattacharjee, Bidisha Paul Chowdhury, Subrata Majumdar* Division of Molecular Medicine, Bose Institute, P1/12, C.I.T. Scheme VII-M, Kolkata, India Abstract The visceral form of leishmaniasis is the most severe form of the disease and of particular concern due to the emerging problem of HIV/visceral leishmaniasis (VL) co-infection in the tropics. Till date miltefosine, amphotericin B and pentavalent antimony compounds remain the main treatment regimens for leishmaniasis. However, because of severe side effects, there is an urgent need for alternative improved therapies to combat this dreaded disease. In the present study, we have used the murine model of leishmaniasis to evaluate the potential role played by soluble leishmanial antigen (SLA) pulsed-CpG-ODN stimulated dendritic cells (SLA-CpG-DCs) in restricting the intracellular leishmanial growth. We found that mice vaccinated with a single dose of SLA-pulsed DC stimulated by CpG-ODN were protected against a subsequent leishmanial challenge and had a dramatic reduction in parasite burden along with the generation of parasite specific cytotoxic T lymphocytes. Moreover, we demonstrate that the induction of protective immunity conferred by SLA-CpG-DCs depends entirely on the CXC chemokine IFN-c-inducible protein 10 (CXCL10; IP-10). CXCL10 is directly involved in the generation of a parasite specific CD8+ T cell-mediated immune response. We observed significant reduction of CD8+ T cells in mice depleted of CXCL10 suggesting a direct role of CXCL10 in the generation of CD8+ T cells in SLA-CpG-DCs vaccinated mice. CXCL10 also contributed towards the generation of perforin and granzyme B, two important cytolytic mediato