Local expression of B7-H1 promotes organ-specific autoimmunity and transplant rejection

J Clin Invest. 2004 Mar;113(5):694-700. doi: 10.1172/JCI19210.


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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adoptive Transfer
  • Animals
  • Autoimmune Diseases / immunology
  • Autoimmunity
  • B7-1 Antigen / biosynthesis*
  • B7-H1 Antigen
  • Blood Glucose / metabolism
  • Blood Proteins*
  • CD3 Complex / biosynthesis
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Division
  • Cytokines / biosynthesis
  • DNA, Complementary / metabolism
  • Diabetes Mellitus, Type 1 / metabolism
  • Fluoresceins / pharmacology
  • Fluorescent Dyes / pharmacology
  • Graft Rejection*
  • Immune Tolerance
  • Islets of Langerhans / metabolism
  • Islets of Langerhans Transplantation / immunology
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Microscopy, Fluorescence
  • Peptides*
  • Recombinant Fusion Proteins / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Succinimides / pharmacology
  • T-Lymphocytes / metabolism
  • Time Factors


  • 5-(6)-carboxyfluorescein diacetate succinimidyl ester
  • B7-1 Antigen
  • B7-H1 Antigen
  • Blood Glucose
  • Blood Proteins
  • CD3 Complex
  • Cd274 protein, mouse
  • Cytokines
  • DNA, Complementary
  • Fluoresceins
  • Fluorescent Dyes
  • Membrane Glycoproteins
  • Peptides
  • Recombinant Fusion Proteins
  • Succinimides