The effect of blockade of tumor necrosis factor alpha on VLA-1+ T-cells in rheumatoid arthritis patients.
The alpha1beta1 integrin, very late antigen (VLA)-1, characterizes collagen adherent interferon (IFN) gamma producing memory T cells in inflamed synovium. We now report that the mean percentage of VLA-1+ T cells is significantly lower among peripheral blood mononuclear cells of rheumatoid patients responsive to antitumor necrosis factor (TNF) alpha therapy than of those with active disease not receiving therapy. Neutralization of TNFalpha during in vitro polyclonal activation of VLA-1- T cells reduced differentiation to expression of VLA-1 and inhibited secretion of IFNgamma, but did not affect integrin expression on in vivo differentiated VLA-1+ T cells. Moreover, synovial fluids of patients relapsing during and after therapy were enriched in VLA-1+ T cells and lines derived from VLA-1+ T cells in peripheral blood of treated patients retained collagen binding and secreted IFN gamma. Thus, whereas therapy decreases VLA-1+ T cells in rheumatoid arthritis patients, a subset is resistant and contributes to residual and recurring inflammation.
Ben-Horin
Shomron
S
Chaim Sheba Medical Center, Tel Hashomer, Israel.
Goldstein
Itamar
I
Koltakov
Alexander
A
Langevitz
Pnina
P
Ehrenfeld
Michael
M
Rosenthal
Esther
E
Gur
Hanan
H
Bank
Ilan
I
D000328:Adult; D000368:Aged; D019138:Antibodies, Blocking / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000276:immunology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy; D002460:Cell Line; D015536:Down-Regulation / Q000276:immunology; D005260:Female; D006801:Humans; D000069285:Infliximab; D039423:Integrin alpha1 / Q000096:biosynthesis* / Q000502:physiology; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D012008:Recurrence; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology
D019138:Antibodies, Blocking; D000911:Antibodies, Monoclonal; D018501:Antirheumatic Agents; D039423:Integrin alpha1; D014409:Tumor Necrosis Factor-alpha; D000069285:Infliximab