Adoptive transfer of NK 1.1+ lymphocytes in immune-mediated colitis: a pro-inflammatory or a tolerizing subgroup of cells?
T lymphocytes expressing NK1.1 marker (NKT) have been suggested to play crucial roles in immune modulation.


OBJECTIVE
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.
Menachem
Yoram
Y
Liver Unit, Department of Medicine, Hadassah University Hospital, Jerusalem, Israel.
Trop
Shivti
S
Kolker
Olga
O
Shibolet
Oren
O
Alper
Ruslana
R
Nagler
Arnon
A
Ilan
Yaron
Y
D019264:Adoptive Transfer; D000818:Animals; D000941:Antigens / Q000502:physiology*; D000950:Antigens, Ly; D000954:Antigens, Surface; D003092:Colitis / Q000276:immunology* / Q000473:pathology; D003106:Colon / Q000473:pathology; D007108:Immune Tolerance; D037181:Lectins, C-Type; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins / Q000502:physiology*; D013154:Spleen / Q000166:cytology; D016176:T-Lymphocyte Subsets / Q000502:physiology*
D000941:Antigens; D000950:Antigens, Ly; D000954:Antigens, Surface; C527211:Klrb1c protein, mouse; D037181:Lectins, C-Type; D055651:NK Cell Lectin-Like Receptor Subfamily B; D011506:Proteins