Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis.
A pathogenic hallmark of rheumatoid arthritis (RA) is persistent activation of self-reactive CD4(+) T cells. The cause of this aberrant activity remains elusive. We report here detection of autoantibodies against B7-H1, a recently described member of the B7 family, in 29% of patients with RA versus 4% of healthy donors. High-level expression of cell surface B7-H1 are found on activated human CD4(+), CD8(+), and CD45RO(+) T cells. Immobilized autoantibodies to B7-H1 are capable of costimulating the proliferation of CD4(+) T cells in vitro, and the presence of these autoantibodies correlates with active disease status. Using immobilized B7-H1 mAb's and programmed death 1Ig, we demonstrate that engagement of B7-H1 on CD4(+) T cells costimulates proliferation and secretion of IL-10, and subsequently leads to programmed cell death, accompanied with upregulated expression of TNF-related apoptosis-inducing ligand and activation of caspase-3. Taken together with our previous findings, these data indicate a bidirectional signaling role of B7-H1 in T cell costimulation and apoptosis and implicate B7-H1 autoantibodies as contributing to the progression of RA by inducing aberrant T cell responses.
Dong
Haidong
H
Department of Immunology, Mayo Medical School and Graduate School, Mayo Clinic, Rochester, Minnesota 55905, USA.
Strome
Scott E
SE
Matteson
Eric L
EL
Moder
Kevin G
KG
Flies
Dallas B
DB
Zhu
Gefeng
G
Tamura
Hideto
H
Driscoll
Colin L W
CL
Chen
Lieping
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D000911:Antibodies, Monoclonal / Q000378:metabolism; D015703:Antigens, CD; D017209:Apoptosis; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D001323:Autoantibodies; D018122:B7-1 Antigen / Q000276:immunology*; D060890:B7-H1 Antigen; D001798:Blood Proteins; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D002455:Cell Division; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000096:biosynthesis; D017493:Leukocyte Common Antigens / Q000096:biosynthesis; D008297:Male; D008562:Membrane Glycoproteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D010455:Peptides; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D013997:Time Factors
D000911:Antibodies, Monoclonal; D015703:Antigens, CD; D001323:Autoantibodies; D018122:B7-1 Antigen; D060890:B7-H1 Antigen; D001798:Blood Proteins; C423236:CD274 protein, human; C498919:Cd274 protein, mouse; D008562:Membrane Glycoproteins; D010455:Peptides; D016753:Interleukin-10; D017493:Leukocyte Common Antigens