title: CD1-dependent natural killer (NK1.1(+)) T cells are required for oral and portal venous tolerance induction.
abstract: BACKGROUND
  Local antigen presentation via either the oral (PO) or the portal venous (PV) routes results in suppression of systemic delayed-type hypersensitivity (DTH). The responsible cell populations are not well defined. Because NK1.1(+) T cells express the Fas ligand and produce high levels of the immunosuppressive cytokine, IL-4, they may play a role in both activated T-cell apoptosis and a Th1 to Th2 immune shift, thus promoting tolerance induction.
  
  
  METHODS
  C57BL/6 mice were tolerized to BALB/c alloantigen by PV or PO spleen cells (25 x 10(6)) on Day 0. Subcutaneous (SQ) challenge with 10 x 10(6) BALB/c cells on Day 7 was followed by footpad injection of 10 x 10(6) BALB/c cells on Day 14. Footpad swelling was measured 24 h later. A single injection of the NK1.1(+) cell-depleting antibody, PK-136, was given IP (10 mg/kg) 2 days prior to PV or PO antigen. Flow cytometry evaluated NK1.1(+) cell depletion. CD1 knockout (KO) mice, lacking NK1.1(+) T cells, were also challenged with PV and PO Balb/c in parallel experiments.
  
  
  RESULTS
  The DTH to BALB/c antigen was markedly suppressed in C57BL/6 mice when this alloantigen was given by either PO or PV routes (P < 0.001, P < 0.001). The maintenance of an unaltered response to third-party C3H/HeJ demonstrated alloantigenic specificity. Administration of the anti-NK1.1 T cell monoclonal antibody, PK-136, resulted in complete restoration of in vivo DTH responsiveness in PO tolerance (P < 0.01), and partial restoration in PV tolerance (P < 0.05) in C57BL/6 mice. FACS confirmed virtually complete depletion of liver, splenic, Peyer's patch, and mesenteric lymph node NK1.1(+) lymphocytes. Development of both PO and PV tolerance was prevented in CD1 KO mice.
  
  
  CONCLUSIONS
  NK1.1(+) T cells play an essential role in antigen-specific suppression of the DTH response mediated by both oral and portal venous tolerance.
authors.affiliation: Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
authors.forename: Julie A
authors.initials: JA
authors.lastname: Margenthaler
authors.forename: Keith
authors.initials: K
authors.lastname: Landeros
authors.forename: Masaaki
authors.initials: M
authors.lastname: Kataoka
authors.forename: M Wayne
authors.initials: MW
authors.lastname: Flye
mesh_terms: D000284:Administration, Oral; D000818:Animals; D018949:Antigens, CD1 / Q000502:physiology*; D017690:Cell Transplantation / Q000379:methods; D006968:Hypersensitivity, Delayed / Q000276:immunology; D007108:Immune Tolerance / Q000502:physiology*; D007275:Injections, Intravenous; D007519:Isoantigens / Q000276:immunology*; D007694:Killer Cells, Natural / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D011169:Portal Vein; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000502:physiology*
chemical_list: D018949:Antigens, CD1; D007519:Isoantigens