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

Yoram Menachem, Shivti Trop, Olga Kolker, Oren Shibolet, Ruslana Alper, Arnon Nagler, Yaron Ilan*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

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+IFNγ+ ratio. In contrast, recipients of splenocytes from NK1.1-depleted-tolerized mice exhibited severe colitis with a significant decrease of the CD4+IL4+/ CD4+IFNγ+ 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+IFNγ+ 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+IFNγ ratio immune-mediated colitis and in peripheral tolerance induction.

Original languageEnglish
Pages (from-to)825-835
Number of pages11
JournalMicrobes and Infection
Volume7
Issue number5-6
DOIs
StatePublished - May 2005
Externally publishedYes

Funding

FundersFunder number
Roaman-Epstein Liver Research Foundation
Israel Cancer Research Fund
Israel Science Foundation

    Keywords

    • Experimental colitis
    • NKT cells
    • Oral tolerance

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