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Deficiencies in gut NK cell number and function precede diabetes onset in BB rats
Authors
Todd, Derrick JamesForsberg, Eric M.
Greiner, Dale L.
Mordes, John P.
Rossini, Aldo A.
Bortell, Rita
UMass Chan Affiliations
Department of Medicine, Diabetes DivisionMorningside Graduate School of Biomedical Sciences
Document Type
Journal ArticlePublication Date
2004-04-22
Metadata
Show full item recordAbstract
Defects in the intestinal immune system may contribute to the pathogenesis of autoimmune diseases. Intraepithelial lymphocytes represent a substantial fraction of gut-associated lymphocytes, but their function in mucosal immunity is unclear. A newly described population of NK cells that spontaneously secrete IL-4 and IFN-gamma is present in the intraepithelial lymphocyte compartment of the rat. We hypothesized that defects in the number or function of these cells would be present in rats susceptible to autoimmunity. We report that the number of NKR-P1A(+)CD3(-) intraepithelial NK (IENK) cells is deficient before onset of spontaneous autoimmune diabetes in diabetes-prone BB (BBDP) rats. The absolute number of recoverable IENK cells was only approximately 8% of that observed in WF rats. Bone marrow transplantation from histocompatible WF donors reversed the IENK cell deficiency (and prevented diabetes) in these animals, suggesting a hemopoietic origin for their IENK cell defect. Analysis of diabetes-resistant BB rats, which develop autoimmune diabetes only after perturbation of the immune system, revealed IENK cell numbers intermediate between that of BBDP and WF rats. IENK cells were selectively depleted during treatment to induce diabetes. Prediabetic BBDP and diabetes-resistant BB animals also exhibited defective IENK cell function, including decreased NK cell cytotoxicity and reduced secretion of IL-4 and IFN-gamma. IENK functional defects were also observed in LEW and BN rats, which are susceptible to induced autoimmunity, but not in WF, DA, or F344 rats, which are resistant. Defects in IENK cell number and function may contribute to the pathogenesis of autoimmune diseases including type 1 diabetes.Source
J Immunol. 2004 May 1;172(9):5356-62.
DOI
10.4049/jimmunol.172.9.5356Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32695PubMed ID
15100275Related Resources
ae974a485f413a2113503eed53cd6c53
10.4049/jimmunol.172.9.5356