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.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Adoptive Transfer
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Animals
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Autoimmune Diseases / immunology
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Autoimmunity
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B7-1 Antigen / biosynthesis*
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B7-H1 Antigen
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Blood Glucose / metabolism
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Blood Proteins*
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CD3 Complex / biosynthesis
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CD8-Positive T-Lymphocytes / metabolism
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Cell Division
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Cytokines / biosynthesis
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DNA, Complementary / metabolism
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Diabetes Mellitus, Type 1 / metabolism
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Fluoresceins / pharmacology
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Fluorescent Dyes / pharmacology
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Graft Rejection*
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Immune Tolerance
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Islets of Langerhans / metabolism
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Islets of Langerhans Transplantation / immunology
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Membrane Glycoproteins
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Microscopy, Fluorescence
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Peptides*
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Recombinant Fusion Proteins / metabolism
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Reverse Transcriptase Polymerase Chain Reaction
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Succinimides / pharmacology
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T-Lymphocytes / metabolism
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Time Factors
Substances
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5-(6)-carboxyfluorescein diacetate succinimidyl ester
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B7-1 Antigen
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B7-H1 Antigen
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Blood Glucose
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Blood Proteins
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CD3 Complex
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Cd274 protein, mouse
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Cytokines
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DNA, Complementary
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Fluoresceins
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Fluorescent Dyes
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Membrane Glycoproteins
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Peptides
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Recombinant Fusion Proteins
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Succinimides