CD8(+) T cell-mediated spontaneous diabetes in neonatal mice.
Transgenic mice that express the influenza virus hemagglutinin (HA) on pancreatic islet beta cells (ins-HA) demonstrate tolerance of HA even after immunization with influenza virus. Surprisingly, when Ins-HA mice were mated with a transgenic mouse expressing a TCR specific for an epitope of HA that is restricted by MHC class I H-2Kd (Clone-4 TCR), the resulting double transgenic (Ins-HA x Clone-4 TCR)F1 neonates developed spontaneous autoimmune diabetes immediately after birth and died within 10 days. This represents a unique situation in which all safeguards within the immune system that normally maintain tolerance of self-antigens in the neonate are insufficient.
Morgan
D J
DJ
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Liblau
R
R
Scott
B
B
Fleck
S
S
McDevitt
H O
HO
Sarvetnick
N
N
Lo
D
D
Sherman
L A
LA
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000276:immunology* / Q000473:pathology; D005434:Flow Cytometry; D006183:H-2 Antigens / Q000276:immunology; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D010179:Pancreas / Q000276:immunology / Q000473:pathology; D011948:Receptors, Antigen, T-Cell / Q000276:immunology; D014759:Viral Envelope Proteins / Q000276:immunology
D006183:H-2 Antigens; C024755:H-2K(K) antigen; D019267:Hemagglutinin Glycoproteins, Influenza Virus; D006389:Hemagglutinins, Viral; D011948:Receptors, Antigen, T-Cell; D014759:Viral Envelope Proteins