Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
Liver-associated lymphocytes expressing NK1.1 are essential for oral immune tolerance induction in a murine model.
Hepatology. 1999 Mar;29(3):746-55. Unique Identifier : AIDSLINE MED/99162365 Trop S; Samsonov D; Gotsman I; Alper R; Diment J; Ilan Y; Liver Unit, Division of Medicine, Hadassah University Hospital,; Jerusalem, Israel.
Abstract:
Oral tolerance is the induction of immunological hyporesponsiveness towards orally administered antigens. Tolerance initiation involves induction of anti-inflammatory (Th2) lymphocytes, with downregulation of pro-inflammatory (Th1) lymphocytes. The liver was previously shown to play a critical role in oral tolerance induction. The aim of the present study was to test whether liver-associated-lymphocytes expressing the NK1.1 marker (NK1.1+ LAL) are substantial for induction of oral tolerance in an experimental colitis model. Colitis was induced in C57 mice by intracolonic instillation of trinitrobenzensulfonic acid (TNBS). Mice received five oral doses of colonic proteins extracted from TNBS-colitis colonic wall. Anti-NK1.1 monoclonal antibodies were injected before tolerance induction. Colitis was assessed by standard clinical, macroscopic, and microscopic scores. Serum IFN-gamma, TGF-beta1, and IL4 levels were measured by enzyme-linked immunosorbent assay. To evaluate the role of NK1.1+ LAL in keeping the balance between immunogenic and tolerogenic subsets of cells, we tested whether peripheral lymphocytes harvested from tolerized and NK1.1-depleted nontolerized mice can adoptively transfer the tolerance into naive irradiated rats. Depletion of NK1.1+ LAL prevented immune tolerance induction in the experimental colitis model. NK1.1+ LAL-depleted nontolerized mice, disclosed severe clinical, macroscopic, and microscopic parameters of colitis. These mice had significantly lower TGF-beta1, IL4, and higher IFN-gamma serum levels, and their lymphocytes failed to transfer the tolerance into naive animals. In contrast, the feeding of colitis-extracted proteins, without NK1.1+ LAL depletion, markedly alleviated the disease. Tolerized mice had higher IL4 and TGF-beta1 and lower IFN-gamma serum levels, and adoptive transfer of their suppressor splenocytes markedly alleviated colitis in naive recipients. NK1.1+ LAL plays a critical role in oral tolerance induction. Depletion of this subset of LAL prevents a shift from Th1 to a Th2 type of immune response, hindering the ability to induce immune tolerance.
Keywords: JOURNAL ARTICLE Administration, Oral Animal Antibody Formation/PHYSIOLOGY Antigens/*ADMINISTRATION & DOSAGE/IMMUNOLOGY/*METABOLISM Biological Markers Colitis/IMMUNOLOGY/PATHOLOGY Cytokines/BLOOD Cytotoxicity, Immunologic/PHYSIOLOGY Immune Tolerance/*PHYSIOLOGY Killer Cells, Natural/*IMMUNOLOGY Liver/*CYTOLOGY Lymphocytes/IMMUNOLOGY/*METABOLISM Male Mice Mice, Inbred C57BL Proteins/IMMUNOLOGY Rats Support, Non-U.S. Gov't T-Lymphocytes, Suppressor-Effector/PHYSIOLOGY Th1 Cells/IMMUNOLOGY Th2 Cells/IMMUNOLOGY 990630
A9960932
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Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.
