Association between alphabetaTCR+CD4-CD8- T-cell deficiency and IDDM in NOD/Lt mice.
NOD mice develop spontaneous IDDM as a result of T-cell-mediated autoimmune destruction of pancreatic beta-cells. It is not known why these T-cells become autoreactive, nor is it clear whether the breakdown in self-tolerance reflects a general problem in T-cell development or a selective defect in an as yet undefined regulatory cell population. In this study, we showed that NOD mice, although relatively normal with regard to most thymocyte subsets, exhibit a marked deficiency in alphabetaTCR+CD4-CD8- (alphabeta+DN) T-cells in the thymus and, to a lesser extent, in the periphery. These T-cells have been termed NKT cells (NK1.1+-like T-cells) because they share some cell surface markers with conventional natural killer (NK) cells. To examine the role of these cells in the pathogenesis of IDDM, semiallogeneic or syngeneic double-negative (DN) thymocytes, enriched for NKT cells, were transferred into intact 4-week-old NOD recipients; the onset of diabetes was then monitored over the ensuing 30 weeks. Mice receiving NKT-enriched thymocytes did not develop diabetes, whereas mice receiving unfractionated thymocytes or phosphate-buffered saline developed diabetes at the normal rate. NKT cells represent a distinct T-cell lineage that has been shown to play a role in immunoregulation in vivo. The deficiency of these cells observed in NOD mice may therefore contribute to destruction of pancreatic islet cells by conventional T-cells.
Baxter
A G
AG
Centenary Institute of Cancer Medicine and Cell Biology, Camperdown, Australia. a.baxter@centenary.usyd.edu.au
Kinder
S J
SJ
Hammond
K J
KJ
Scollay
R
R
Godfrey
D I
DI
D019264:Adoptive Transfer; D000375:Aging / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D015704:CD4 Antigens / Q000032:analysis* / Q000276:immunology; D016516:CD4-CD8 Ratio; D016827:CD8 Antigens / Q000032:analysis* / Q000276:immunology; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D005434:Flow Cytometry; D015994:Incidence; D017493:Leukocyte Common Antigens / Q000032:analysis / Q000276:immunology; D051379:Mice; D008815:Mice, Inbred Strains; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D011817:Rabbits; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000032:analysis* / Q000276:immunology; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000737:chemistry* / Q000166:cytology / Q000276:immunology
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D016693:Receptors, Antigen, T-Cell, alpha-beta; D017493:Leukocyte Common Antigens; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1