Regulation of autoimmune diabetes by complete Freund's adjuvant is mediated by NK cells.
Autoimmune (type 1) diabetes results from a loss of beta cells that is mediated by self-reactive T cells. Previous studies have shown that a single injection of CFA prevents diabetes in nonobese diabetic (NOD) mice, but the mechanism(s) of protection remain unknown. We show here that NOD mice immunized with CFA have a markedly reduced incidence of diabetes and that this reduced incidence is associated with a decrease in the number of beta cell-specific, autoreactive CTL. In addition, the adoptive transfer of diabetes into syngeneic NOD/SCID recipients was prevented by CFA immunization, and the protective effects of CFA were lost when cells expressing the NK cell marker, asialo GM1, were removed from both donor cells and recipient mice. Returning a population of CD3-DX5+ cells to the adoptive transfer restored the protective effects of CFA. Therefore, NK cells mediate the protective effects of CFA possibly through the down-regulation of autoreactive CTL and stimulation of NK cells represents a novel approach to the prevention of autoimmune diabetes.
Lee
I-Fang
IF
Department of Pathology & Laboratory Medicine, British Columbia's Children's Hospital and University of British Columbia, 4480 Oak Street, Vancouver, BC V6H 2V4, Canada.
Qin
Huilian
H
Trudeau
Jacqueline
J
Dutz
Jan
J
Tan
Rusung
R
D019264:Adoptive Transfer; D000818:Animals; D002449:Cell Aggregation / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000473:pathology / Q000517:prevention & control; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D005620:Freund's Adjuvant / Q000008:administration & dosage* / Q000276:immunology*; D007371:Interferon-gamma / Q000378:metabolism; D007515:Islets of Langerhans / Q000276:immunology / Q000473:pathology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D018655:Lymphocyte Count; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D011236:Prediabetic State / Q000276:immunology / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000637:transplantation; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology
D007371:Interferon-gamma; D005620:Freund's Adjuvant