(Journal Article): Local expression of B7-H1 promotes organ-specific autoimmunity and transplant rejection.
 
Subudhi SK, Zhou P, Yerian LM, Chin RK, Lo JC, Anders RA, Sun Y, Chen L, Wang Y, Alegre ML, Fu YX (Committee on Immunology, University of Chicago, Chicago, Illinois 60637, USA.)
 
IN: J Clin Invest 2004; 113(5):694-700
Impact Factor(s) of J Clin Invest: 14.204 (2004), 14.307 (2003), 14.118 (2001)

Fulltext:    HTML  PDF

ABSTRACT: A number of studies have suggested B7-H1, a B7 family member, inhibits T cell responses. Therefore, its expression on nonlymphoid tissues has been proposed to prevent T cell-mediated tissue destruction. To test this hypothesis, we generated transgenic mice that expressed B7-H1 on pancreatic islet beta cells. Surprisingly, we observed accelerated rejection of transplanted allogeneic B7-H1-expressing islet beta cells. Furthermore, transgenic B7-H1 expression broke immune tolerance, as some of the mice spontaneously developed T cell-dependent autoimmune diabetes. In addition, B7-H1 expression increased CD8+ T cell proliferation and promoted autoimmunity induction in a T cell adoptive transfer model of diabetes. Consistent with these findings, B7-H1.Ig fusion protein augmented naive T cell priming both in vitro and in vivo. Our results demonstrate that B7-H1 can provide positive costimulation for naive T cells to promote allograft rejection and autoimmune disease pathogenesis.

TYPE OF PUBLICATION: Original article

Articles citing this article:

• Yadav D, Sarvetnik N. Costimulation and Pancreatic Autoimmunity: The PD-1/PD-L Conundrum. Rev Diabetic Stud 2006. 3: 6-10.
  » Diabetes OD » Development and Function of Pa... » Immune System » Activation and Inhibition » Costimulation » Programmed Death » Journal Article