Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis

Haidong M Dong, Scott E. Strome, Eric Lawrence Matteson, Kevin G. Moder, Dallas B. Flies, Gefeng Zhu, Hideto Tamura, Colin L W Driscoll, Lieping Chen

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)363-370
Number of pages8
JournalJournal of Clinical Investigation
Volume111
Issue number3
DOIs
StatePublished - Feb 2003

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Autoantibodies
Rheumatoid Arthritis
T-Lymphocytes
TNF-Related Apoptosis-Inducing Ligand
Caspase 3
Interleukin-10
Cell Death
Cell Proliferation
Tissue Donors
Apoptosis

ASJC Scopus subject areas

  • Medicine(all)

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Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis. / Dong, Haidong M; Strome, Scott E.; Matteson, Eric Lawrence; Moder, Kevin G.; Flies, Dallas B.; Zhu, Gefeng; Tamura, Hideto; Driscoll, Colin L W; Chen, Lieping.

In: Journal of Clinical Investigation, Vol. 111, No. 3, 02.2003, p. 363-370.

Research output: Contribution to journalArticle

Dong, HM, Strome, SE, Matteson, EL, Moder, KG, Flies, DB, Zhu, G, Tamura, H, Driscoll, CLW & Chen, L 2003, 'Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis', Journal of Clinical Investigation, vol. 111, no. 3, pp. 363-370. https://doi.org/10.1172/JCI200316015
Dong, Haidong M ; Strome, Scott E. ; Matteson, Eric Lawrence ; Moder, Kevin G. ; Flies, Dallas B. ; Zhu, Gefeng ; Tamura, Hideto ; Driscoll, Colin L W ; Chen, Lieping. / Costimulating aberrant T cell responses by B7-H1 autoantibodies in rheumatoid arthritis. In: Journal of Clinical Investigation. 2003 ; Vol. 111, No. 3. pp. 363-370.
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