A CD8+ T-lymphocyte-mediated and CD4+ T-lymphocyte-independent autoimmune diabetes of early onset in transgenic mice.
While transgenic mice expressing tumour necrosis factor-alpha under the control of the beta-cell-specific insulin promoter display a marked lymphocytic infiltration of the islets, they never develop insulin-dependent diabetes mellitus (IDDM). In striking contrast, "double" transgenic mice whose beta cells express both tumour necrosis factor-alpha as well as the co-stimulatory B7-1 molecule all develop IDDM at an early age. Furthermore, administration of anti-CD8 but not anti-CD4 immunoglobulins prevents diabetes onset. These results indicate that while tumour necrosis factor-alpha induced lymphocytic infiltration is not sufficient to effect beta-cell destruction, locally co-stimulated islet-infiltrating CD8+ T lymphocytes could play a critical role in the development of IDDM.
Herrera
P L
PL
Department of Morphology, University of Geneva Medical School, Switzerland.
Harlan
D M
DM
Fossati
L
L
Izui
S
S
Huarte
J
J
Orci
L
L
Vassalli
J D
JD
Vassalli
P
P
D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology* / Q000517:prevention & control; D018122:B7-1 Antigen / Q000096:biosynthesis* / Q000276:immunology; D001786:Blood Glucose / Q000378:metabolism; D015704:CD4 Antigens / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016827:CD8 Antigens / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology* / Q000517:prevention & control; D005260:Female; D016756:Immunoglobulins, Intravenous / Q000494:pharmacology; D007515:Islets of Langerhans / Q000276:immunology; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000276:immunology
D018122:B7-1 Antigen; D001786:Blood Glucose; D015704:CD4 Antigens; D016827:CD8 Antigens; D016756:Immunoglobulins, Intravenous; D014409:Tumor Necrosis Factor-alpha