Pancreatic infiltration but not diabetes occurs in the relative absence of MHC class II-restricted CD4 T cells: studies using NOD/CIITA-deficient mice.
The NOD (nonobese diabetic) mouse is a good animal model for human IDDM. MHC class II-restricted CD4 T cells are necessary for the onset of diabetes in NOD mice. Here, we demonstrate that NOD mice lacking the CIITA (class II transactivator) molecule, and hence deficient in MHC class II expression and peripheral CD4 T cells, show significant pancreatic infiltration but do not develop diabetes. CD4 T cell deficiency, then, does not prevent initial pancreatic infiltration, but does stop progression to insulitis. Adoptive transfer studies show that the paucity of CD4 T cells in NOD-CIITA knockout mice is responsible for the absence of diabetes, since the CD8 T cell and B cell compartments are functional. An autoaggressive CD8+ T cell clone can, however, transfer diabetes in CIITA knockout recipient mice without CD4 T cell help, albeit with some delay compared with that in CIITA-sufficient recipients. This highlights the fact that a high number of in vitro activated autoaggressive CD8 T cells can over-ride the requirement for CD4 T cell help for the onset of diabetes.
Mora
C
C
Section of Immunobiology, Yale University School of Medicine, Howard Hughes Medical Institute, New Haven, CT 06520, USA.
Wong
F S
FS
Chang
C H
CH
Flavell
R A
RA
D019264:Adoptive Transfer; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism / Q000473:pathology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000276:immunology*; D002999:Clone Cells / Q000637:transplantation; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology* / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000276:immunology*; D008213:Lymphocyte Activation / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D018345:Mice, Knockout; D016513:Mice, SCID; D009687:Nuclear Proteins; D010179:Pancreas / Q000276:immunology* / Q000473:pathology; D013154:Spleen / Q000166:cytology / Q000637:transplantation; D016176:T-Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015534:Trans-Activators / Q000172:deficiency* / Q000235:genetics*
D000949:Histocompatibility Antigens Class II; C083728:MHC class II transactivator protein; D009687:Nuclear Proteins; D015534:Trans-Activators