Local expression of B7-H1 promotes organ-specific autoimmunity and transplant rejection.
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.
Committee on Immunology, University of Chicago, Chicago, Illinois 60637, USA.
Sumit K
SK
Subudhi
Ping
P
Zhou
Lisa M
LM
Yerian
Robert K
RK
Chin
James C
JC
Lo
Robert A
RA
Anders
Yonglian
Y
Sun
Lieping
L
Chen
Yang
Y
Wang
Maria-Luisa
ML
Alegre
Yang-Xin
YX
Fu
D019264:Adoptive Transfer; D000818:Animals; D001327:Autoimmune Diseases / Q000276:immunology; D015551:Autoimmunity; D018122:B7-1 Antigen / Q000096:biosynthesis*; D060890:B7-H1 Antigen; D001786:Blood Glucose / Q000378:metabolism; D001798:Blood Proteins; D017252:CD3 Complex / Q000096:biosynthesis; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002455:Cell Division; D016207:Cytokines / Q000096:biosynthesis; D018076:DNA, Complementary / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000378:metabolism; D005452:Fluoresceins / Q000494:pharmacology; D005456:Fluorescent Dyes / Q000494:pharmacology; D006084:Graft Rejection; D007108:Immune Tolerance; D007515:Islets of Langerhans / Q000378:metabolism; D016381:Islets of Langerhans Transplantation / Q000276:immunology; D008562:Membrane Glycoproteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D010455:Peptides; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013388:Succinimides / Q000494:pharmacology; D013601:T-Lymphocytes / Q000378:metabolism; D013997:Time Factors
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001786:Blood Glucose; D001798:Blood Proteins; D017252:CD3 Complex; C498919:Cd274 protein, mouse; D016207:Cytokines; D018076:DNA, Complementary; D005452:Fluoresceins; D005456:Fluorescent Dyes; D008562:Membrane Glycoproteins; D010455:Peptides; D011993:Recombinant Fusion Proteins; D013388:Succinimides