CD1-dependent natural killer (NK1.1+) T cells are required for oral and portal venous tolerance induction

Julie A. Margenthaler, Keith Landeros, Masaaki Kataoka, M. Wayne Flye

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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 × 106) on Day 0. Subcutaneous (SQ) challenge with 10 × 106 BALB/c cells on Day 7 was followed by footpad injection of 10 × 106 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. Conclusion. NK1.1+ T cells play an essential role in antigen-specific suppression of the DTH response mediated by both oral and portal venous tolerance.

Original languageEnglish
Pages (from-to)29-35
Number of pages7
JournalJournal of Surgical Research
Issue number1
StatePublished - 2002


  • Delayed-type hypersensitivity
  • Natural killer cells
  • Oral tolerance
  • Portal venous tolerance


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