Adoptive transfer of NK 1.1+ lymphocytes in immune-mediated colitis: a pro-inflammatory or a tolerizing subgroup of cells?

Microbes Infect. 2005 May;7(5-6):825-35. doi: 10.1016/j.micinf.2005.03.019. Epub 2005 Apr 19.

Abstract

T lymphocytes expressing NK1.1 marker (NKT) have been suggested to play crucial roles in immune modulation.

Aim: To determine the role of NK1.1+ cells in induction and maintenance of pro-inflammatory and/or tolerizing responses.

Methods: Colitis was induced in C57/B6 donor mice by intracolonic instillation of trinitrobenzenesulfonic acid (TNBS). Donor mice received five oral doses of colonic proteins extracted from TNBS-colitis colonic wall. Depletion of NK1.1+ lymphocytes was performed before lymphocyte harvesting. Splenocytes were harvested and separated into T-cell subpopulations, and transplanted into recipient mice before intracolonic instillation of TNBS. Standard clinical, macroscopic, and microscopic scores, and intracellular staining, flow cytometry, and cytotoxicity assays were performed.

Results: The adoptive transfer of CD4+ and NK1.1+ cells harvested from tolerized mice markedly ameliorated the colitis in recipient mice. In contrast, the adoptive transfer of CD8+ and double negative lymphocytes failed to transfer the tolerance. Recipients of splenocytes from tolerized mice exhibited an increase in CD4+ IL4+/CD4+ IFNgamma+ ratio. In contrast, recipients of splenocytes from NK1.1-depleted-tolerized mice exhibited severe colitis with a significant decrease of the CD4+ IL4+/CD4+ IFNgamma+ ratio. However adoptive transfer of splenocytes from non-tolerized NKT-depleted mice led to an alleviation of colitis with a relative increase of the CD4+ IL4+/CD4+ IFNgamma+ ratio.

Conclusions: NK1.1+ lymphocytes play a critical role in immune regulation. They may be accountable for an alteration of the inflammatory response and the CD4+ IL4+/CD4+ IFNgamma ratio immune-mediated colitis and in peripheral tolerance induction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens / physiology*
  • Antigens, Ly
  • Antigens, Surface
  • Colitis / immunology*
  • Colitis / pathology
  • Colon / pathology
  • Immune Tolerance
  • Lectins, C-Type
  • Male
  • Mice
  • Mice, Inbred C57BL
  • NK Cell Lectin-Like Receptor Subfamily B
  • Proteins / physiology*
  • Spleen / cytology
  • T-Lymphocyte Subsets / physiology*

Substances

  • Antigens
  • Antigens, Ly
  • Antigens, Surface
  • Klrb1c protein, mouse
  • Lectins, C-Type
  • NK Cell Lectin-Like Receptor Subfamily B
  • Proteins