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

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

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.

Authors

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

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Preferential expression of B7-H1 mAb on activated CD4+ T cells. (a) On t...
Preferential expression of B7-H1 mAb on activated CD4+ T cells. (a) On the left, 293 cells were transfected with mock (pcDNA3 vector) or human B7-H1 plasmid (pcDNA3-B7-H1cDNA) for 48 hours. B7-H1/293 cells were pretreated with 20 μg of control Ig (mIgG1) or 5H1 before staining with PD-1Ig (5 μg). On the right, activated M99 CTL cells were pretreated with 10 μg of mIgG1 or 5H1 before staining with B7-H1Ig (10 μg). B7-H1 mAb, PD-1Ig, or B7-H1Ig were used to stain the transfected 293 cells and activated M99 CTL cells. Representative fluorescence histograms of isotype control reagents (open lines) and B7-H1 mAb or fusion proteins (filled lines) are shown. (b) Induction of B7-H1 expression on human T cell subsets. Human PBMCs were activated with PHA for indicated times and subjected to FACS analysis with B7-H1 mAb and mAb to CD4, CD8, or CD45RO. The numbers indicate the percentage of B7-H1 and CD4, CD8, or CD45RO double-positive cells in total populations, and the percentage in parentheses indicates the percentage of B7-H1–positive cells in each CD4+, CD8+, or CD45RO+ subsets.