Expression of the co-stimulator molecule B7-1 in pancreatic beta-cells accelerates diabetes in the NOD mouse.
B7-1 is a co-stimulatory molecule that signals T-cells that recognize antigen to proliferate and differentiate into effector T-cells. The same cell must present antigen and express co-stimulatory molecules, such as B7-1, to activate naive T-cells. Thus, tissues that do not express co-stimulatory molecules would not be expected to induce immune responses, while expression of a co-stimulator on tissue cells may convert them into effective antigen-presenting cells and induce autoimmunity. To test this, transgenic mice have been generated that express B7-1 on the beta-cells of the pancreatic islets of Langerhans. On a B6 genetic background, B7-1 expression on beta-cells does not predispose to diabetes. B6 mice are resistant to diabetes. However, when B7-1 is expressed on the beta-cells of B6 mice backcrossed once to the genetically susceptible NOD strain, the onset of diabetes is accelerated and the autoimmune attack intensified. This illustrates that B7-1 is a very potent co-stimulatory molecule in vivo and that its presence on the surface of tissue cells can potentiate the autoimmune process.
Wong
S
S
Section of Immunobiology, Yale University School of Medicine, New Haven, Connecticut 06520-8011.
Guerder
S
S
Visintin
I
I
Reich
E P
EP
Swenson
K E
KE
Flavell
R A
RA
Janeway
C A
CA
D000375:Aging / Q000502:physiology; D000818:Animals; D018122:B7-1 Antigen / Q000096:biosynthesis*; D003433:Crosses, Genetic; D003922:Diabetes Mellitus, Type 1 / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007515:Islets of Langerhans / Q000254:growth & development / Q000378:metabolism* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016688:Mice, Inbred NOD; D008822:Mice, Transgenic; D010179:Pancreas / Q000254:growth & development / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*
D018122:B7-1 Antigen