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

J Clin Invest. 2003 Feb;111(3):363-70. doi: 10.1172/JCI16015.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Animals
  • Antibodies, Monoclonal / metabolism
  • Antigens, CD
  • Apoptosis
  • Arthritis, Rheumatoid / immunology*
  • Autoantibodies*
  • B7-1 Antigen / immunology*
  • B7-H1 Antigen
  • Blood Proteins*
  • CD4-Positive T-Lymphocytes / metabolism
  • CD8-Positive T-Lymphocytes / metabolism
  • Cell Division
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Interleukin-10 / biosynthesis
  • Leukocyte Common Antigens / biosynthesis
  • Male
  • Membrane Glycoproteins
  • Mice
  • Mice, Inbred BALB C
  • Middle Aged
  • Peptides*
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism
  • Time Factors


  • Antibodies, Monoclonal
  • Antigens, CD
  • Autoantibodies
  • B7-1 Antigen
  • B7-H1 Antigen
  • Blood Proteins
  • CD274 protein, human
  • Cd274 protein, mouse
  • Membrane Glycoproteins
  • Peptides
  • Interleukin-10
  • Leukocyte Common Antigens