The role of CD1d1 molecules and NKT cells in antiviral immunity.

摘要

The immune response involves a complex interplay between antigen presenting cells and effector cells in host defense against invading pathogens. Classically, studies involving antigen processing and presentation have focused on the role of the major histocompatibility complex (MHC) class I and II molecules in host defense. However, unlike the MHC class I and class II molecules that present peptide antigens to T cells, a novel pathway of lipid antigen presentation has been revealed. CD1d1 molecules present glycolipids and phospholipids to a unique subpopulation of T cells called natural killer T (NKT) cells. NKT cells produce both T helper (Th)1 and Th2 cytokines and appear to be important in regulating immune responses to tumors, as well as infectious and autoimmune diseases. The ability of these cells to rapidly produce cytokines, activate cells of both the innate and adaptive immune responses, and recognize antigen in the context of CD1d1 molecules suggest that NKT cells may also play a pivotal role in antiviral immunity. The hypothesis tested in these studies was that CD1d1 molecules play a direct (via antigen presentation) and/or indirect (via the regulation of NKT cells) role in antiviral host defense. To address this hypothesis, the mechanisms by which CD1d1 molecules associate with their ligands and present them to NKT cells were analyzed, the effects of a virus infection on CD1d1-mediated antigen presentation were examined, and viral immunopathogenesis in normal and CD1d1-deficient mice was investigated. It was found that recycling CD1d1 molecules present endogenous antigens that are processed in endocytic compartments. The data also demonstrate that a vaccinia virus (VV) infection rapidly inhibits CD1d1-mediated antigen presentation (in vitro) and results in the selective loss of NKT cells (in vivo). Collectively, these data implicate an important role for NKT cells and CD1d1 molecules in antiviral host defense and suggest that viruses may have developed unique mechanisms to evade the NKT cell/CD1d1 system.