+ Site Statistics
+ Search Articles
+ PDF Full Text Service
How our service works
Request PDF Full Text
+ Follow Us
Follow on Facebook
Follow on Twitter
Follow on LinkedIn
+ Subscribe to Site Feeds
Most Shared
PDF Full Text
+ Translate
+ Recently Requested

Liver-associated lymphocytes expressing NK1.1 are essential for oral immune tolerance induction in a murine model



Liver-associated lymphocytes expressing NK1.1 are essential for oral immune tolerance induction in a murine model



Hepatology 29(3): 746-755



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.

Please choose payment method:






(PDF emailed within 0-6 h: $19.90)

Accession: 010929289

Download citation: RISBibTeXText

PMID: 10051476

DOI: 10.1002/hep.510290334


Related references

Liver-mediated immunemodulation in a murine model The role of NK11+ liver associated lymphocytes in peripheral tolerance induction. Hepatology 30(4 Part 2): 495A, 1999

Induction of oral immune tolerance in systemic lupus erythematosus-like murine model by recombinant nucleosomal universal Th cell epitope. Zhonghua Yi Xue Za Zhi 89(24): 1702-1706, 2009

Effect of peripheral immune tolerance on liver-associated lymphocytes expressing NK1.1. Transplantation Proceedings 32(4): 749-750, 2000

Oral tolerance in a murine model of relapsing experimental autoimmune uveoretinitis (EAU): Induction of protective tolerance in primed animals. Clinical and Experimental Immunology 109(2): 370-376, 1997

Induction of oral tolerance by CpG-ODNs in a murine model of asthma. Journal of Allergy & Clinical Immunology 113(2 Suppl.): S254, 2004

Oral carrageenan induces antigen-dependent oral tolerance: prevention of anaphylaxis and induction of lymphocyte anergy in a murine model of food allergy. Pediatric Research 49(3): 417-422, 2001

Enhancement of immune tolerance via induction of NK1.1 positive liver-associated-lymphocytes under immunosuppressive conditions. Journal of Hepatology 32(5): 812-820, 2000

Induction of oral tolerance towards hepatitis B envelope antigens in a murine model. Antiviral Research 48(1): 17-26, 2000

Genetic induction of immune tolerance to factor VIII in a murine model for hemophilia A. Blood 90(10 Suppl. 1 Part 1): 240A, 1997

Murine model of oral tolerance. Induction of Fas-mediated apoptosis by blockade of interleukin-12. Annals of the new York Academy of Sciences 859: 290-294, 1998

Interleukin-2 treatment potentiates induction of oral tolerance in a murine model of autoimmunity. Journal of Clinical Investigation 94(4): 1668-1672, 1994

Tolerance induction to a mammalian blood group-like carbohydrate antigen by syngeneic lymphocytes expressing the antigen, II: tolerance induction on memory B cells. Blood 102(1): 229-236, 2003