The role of LIGHT a member of the TNFSF in regulation of secondary immunity to Leishmania major (P3344)

Abstract

Abstract We previously showed that LIGHT, (lymphotoxin like, exhibits inducible expression and competes with HSV glycoprotein D for HVEM, a receptor expressed by T lymphocytes) and its receptors are critically important for initiation of CD4+ T helper (Th1) cell response and development of primary immunity to Leishmania major infection in mice. Here, we further characterized the contributions of this molecule in the activation of dendritic cells (DCs), L. major-induced IL-12 production and secondary anti-Leishmania immunity. We show that blockade of LIGHT significantly impaired DC maturation and expression of costimulatory molecules including, CD40 and CD86. In addition, blockade of LIGHT signaling lead to impairment in L. major-induced IL-12p40 production by DCs in vivo and a concomitant reduction in the number of cells recruited into the draining lymph nodes as well as early IFN-γ production by CD4+ T cells following L. major infection. Furthermore, we show that LIGHT is required at both priming and maintenance stages of anti-Leishmania immunity. Interestingly, blockade of LIGHT had no effect on delayed-type hypersensitivity (DTH) response and control of parasite burden following secondary L. major challenge. Collectively, these results show that LIGHT is critical for IL-12 production by DCs and subsequent priming and maintenance of IFN-γ response by CD4+ T cells during primary but is dispensable during secondary anti-Leishmania immunity.