TY - JOUR
T1 - HLA-DR4Dw4-restricted T cell recognition of self antigen(s) in the rheumatoid synovial compartment
AU - Devereux, Deirdre
AU - O'hehir, Robyn E.
AU - Mcguire, James
AU - Van Schooten, Wim C.A.
AU - Lamb, Jonathan R.
AU - Steinman, L.
PY - 1991/7/1
Y1 - 1991/7/1
N2 - The pathogenesis of joint destruction in rheumatoid arthritis remains III defined, although It is thought to be the result of tissue damage mediated by T cells. This prompted us to isolate and characterize in vivo activated T cells from rheumatoid arthritis synovial fluid in an attempt to determine their specificity. Heterogeneous synovial fluid cells, containing both adherent and non-adherent cell types, were recovered from joint aspirates and cultured in thepresence of IL-2. After 2 weeks, the non-adherent cells were phenotyped as CD3-positive and TCR αβ-positive T cells. Polyclonal T cell lines were derived from four rheumatoid arthritis patients; of these, two proliferated, in a dose-dependent manner to only autologous synovial fluid in the presence of autologous or DR4Dw4 histocompatible antigen presenting cells. T cell proliferation to the synovial fluid could be inhibited by monomorphlc anti-HLA-DR monoclonal antibody, but not by anti-DQ or anti-class I antibodies. T cell clones were established by limiting dilution of a synovial T cell line in the presence of autologous synovial fluid and DR4Dw4 histocompatible accessory cells. Examination of the antigen specificity of these T cell clones demonstrated that they were reactive with a component of synovial fluid. The resultsof these experiments suggest the presence of an MHC class ll-restricted antigen in the rheumatoid arthritis synovial compartment that induces proliferation of in vivo activated T cells.
AB - The pathogenesis of joint destruction in rheumatoid arthritis remains III defined, although It is thought to be the result of tissue damage mediated by T cells. This prompted us to isolate and characterize in vivo activated T cells from rheumatoid arthritis synovial fluid in an attempt to determine their specificity. Heterogeneous synovial fluid cells, containing both adherent and non-adherent cell types, were recovered from joint aspirates and cultured in thepresence of IL-2. After 2 weeks, the non-adherent cells were phenotyped as CD3-positive and TCR αβ-positive T cells. Polyclonal T cell lines were derived from four rheumatoid arthritis patients; of these, two proliferated, in a dose-dependent manner to only autologous synovial fluid in the presence of autologous or DR4Dw4 histocompatible antigen presenting cells. T cell proliferation to the synovial fluid could be inhibited by monomorphlc anti-HLA-DR monoclonal antibody, but not by anti-DQ or anti-class I antibodies. T cell clones were established by limiting dilution of a synovial T cell line in the presence of autologous synovial fluid and DR4Dw4 histocompatible accessory cells. Examination of the antigen specificity of these T cell clones demonstrated that they were reactive with a component of synovial fluid. The resultsof these experiments suggest the presence of an MHC class ll-restricted antigen in the rheumatoid arthritis synovial compartment that induces proliferation of in vivo activated T cells.
KW - Autoimmunity
KW - Rheumatoid arthritis
KW - T cells
UR - http://www.scopus.com/inward/record.url?scp=0025799936&partnerID=8YFLogxK
U2 - 10.1093/intimm/3.7.635
DO - 10.1093/intimm/3.7.635
M3 - Article
C2 - 1911537
AN - SCOPUS:0025799936
SN - 0953-8178
VL - 3
SP - 635
EP - 640
JO - International Immunology
JF - International Immunology
IS - 7
ER -