title: dysregulation of CD1d-restricted type ii natural killer T cells leads to spontaneous development of colitis in mice.
abstract: OBJECTIVE
  CD1d-restricted natural killer (NK) T cells are a subset of immunoregulatory T cells that comprise type I (express the semi-invariant T-cell receptor [TCR] and can be detected using the α-galactosylceramide/CD1d tetramer) and type II (express diverse TCRs and cannot be directly identified). Studies in mouse models of inflammatory bowel disease revealed a complex role for type I NKT cells in the development of colitis. Type II NKT cells have been associated with intestinal inflammation in patients with ulcerative colitis.
  
  
  METHODS
  To investigate whether dysregulation of type II NKT cells, caused by increased expression of CD1d, can contribute to colitis, we generated transgenic mice that express high levels of CD1d and a TCR from an autoreactive, type II NKT cell (CD1dTg/24αβTg mice).
  
  
  RESULTS
  CD1dTg/24αβTg mice had reduced numbers of 24αβ T cells compared with 24αβTg mice, indicating that negative selection increases among type II NKT cells engaged by abundant self-antigen. The residual 24αβ T cells in CD1dTg/24αβTg mice had an altered surface phenotype and acquired a cytokine profile distinct from that of equivalent cells in 24αβTg mice. Interestingly, CD1dTg/24αβTg mice spontaneously developed colitis; adoptive transfer experiments confirmed that type II NKT cells that develop in the context of increased CD1d expression are pathogenic.
  
  
  CONCLUSIONS
  Aberrant type II NKT cell responses directly contribute to intestinal inflammation in mice, indicating the importance of CD1d expression levels in the development and regulation of type II NKT cells.
authors: Department of Microbiology and Immunology, Northwestern University, Chicago, Illinois 60611, USA.
authors: Chia-Min
authors: CM
authors: Liao
authors: Michael I
authors: MI
authors: Zimmer
authors: Sharmila
authors: S
authors: Shanmuganad
authors: Hon-Tsen
authors: HT
authors: Yu
authors: Susanna L
authors: SL
authors: Cardell
authors: Chyung-Ru
authors: CR
authors: Wang
mesh_terms: D000818:Animals; D055610:Antigens, CD1d / Q000378:metabolism*; D003093:Colitis, Ulcerative / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005434:Flow Cytometry; D051379:Mice; D008822:Mice, Transgenic; D055611:Natural Killer T-Cells / Q000378:metabolism*
chemical_list: D055610:Antigens, CD1d; C526879:Cd1d1 protein, mouse; D016207:Cytokines