Institution: | 1. Division of Gastroenterology and Hepatology, Hepatitis C Center, Department of Medicine, University of Colorado Denver (UCD), Aurora, CO 80045, USA;2. Pediatric Gastroenterology, Digestive Health Institute, Children''s Hospital Colorado, Aurora, CO, USA;3. Denver VA Medical Center, Denver, CO, USA;1. Division of Comparative Pathology, Tulane National Primate Research Center, Covington, LA, USA;2. Tulane University School of Medicine, New Orleans, LA, USA;3. Division of Microbiology, Tulane National Primate Research Center, Covington, LA, USA |
Abstract: | Lupus is a systemic autoimmune disease characterized by anti-nuclear antibodies in humans and genetically susceptible NZB/W mice that can cause immune complex glomerulonephritis. T cells contribute to lupus pathogenesis by secreting pro-inflammatory cytokines such as IL-17, and by interacting with B cells and secreting helper factors such as IL-21 that promote production of IgG autoantibodies. In the current study, we determined whether purified NKT cells or far more numerous conventional non-NKT cells in the spleen of NZB/W female mice secrete IL-17 and/or IL-21 after TCR activation in vitro, and provide help for spontaneous IgG autoantibody production by purified splenic CD19+ B cells. Whereas invariant NKT cells secreted large amounts of IL-17 and IL-21, and helped B cells, non-NKT cells did not. The subset of IL-17 secreting NZB/W NKT cells expressed the Ly108loCD4?NK1.1? phenotype, whereas the IL-21 secreting subset expressed the Ly108hiCD4+NK1.1? phenotype and helped B cells secrete a variety of IgG anti-nuclear antibodies. α-galactocylceramide enhanced the helper activity of NZB/W and B6.Sle1b NKT cells for IgG autoantibody secretion by syngeneic B cells. In conclusion, different subsets of iNKT cells from mice with genetic susceptibility to lupus can contribute to pathogenesis by secreting pro-inflammatory cytokines and helping autoantibody production. |