Beta 2-microglobulin-deficient NOD mice do not develop insulitis or diabetes.
The role of CD8+ T-cells in the development of diabetes in the nonobese diabetic (NOD) mouse remains controversial. Although it is widely agreed that class II-restricted CD4+ T-cells are essential for the development of diabetes in the NOD model, some studies have suggested that CD8+ T-cells are not required for beta-cell destruction. To assess the contribution of CD8+ T-cells to diabetes, we have developed a class of NOD mouse that lacks expression of beta 2-microglobulin (NOD-B2mnull). NOD-B2mnull mice, which lack both class I expression and CD8+ T-cells in the periphery, not only failed to develop diabetes but were completely devoid of insulitis. These results demonstrate an essential role for CD8+ T-cells in the initiation of the autoimmune response to beta-cells in the NOD mouse.
Wicker
L S
LS
Department of Autoimmune Diseases Research, Merck Research Laboratories, Rahway, New Jersey 07065-0900.
Leiter
E H
EH
Todd
J A
JA
Renjilian
R J
RJ
Peterson
E
E
Fischer
P A
PA
Podolin
P L
PL
Zijlstra
M
M
Jaenisch
R
R
Peterson
L B
LB
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology*; D001483:Base Sequence; D016827:CD8 Antigens / Q000032:analysis; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D005260:Female; D007515:Islets of Langerhans / Q000276:immunology; D051379:Mice; D016688:Mice, Inbred NOD; D008969:Molecular Sequence Data; D013154:Spleen / Q000166:cytology; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation; D001613:beta 2-Microglobulin / Q000172:deficiency* / Q000235:genetics
D016827:CD8 Antigens; D001613:beta 2-Microglobulin