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Clinical and Diagnostic Laboratory Immunology, January 2004, p. 195-202, Vol. 11, No. 1
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.1.195-202.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Decreased Expression of the CD3{zeta} Chain in T Cells Infiltrating the Synovial Membrane of Patients with Osteoarthritis

Lazaros I. Sakkas,1,{dagger} George Koussidis,1,{dagger} Efthimios Avgerinos,1,{dagger} John Gaughan,2 and Chris D. Platsoucas1*

Department of Microbiology and Immunology,1 Department of Physiology (Biostatistics), Temple University School of Medicine, Philadelphia, Pennsylvania 191402

Received 24 April 2003/ Returned for modification 16 July 2003/ Accepted 2 October 2003

Osteoarthritis (OA) is a heterogeneous disease which rheumatologists consider to be noninflammatory. However, recent studies suggest that, at least in certain patients, OA is an inflammatory disease and that patients often exhibit inflammatory infiltrates in the synovial membranes (SMs) of macrophages and activated T cells expressing proinflammatory cytokines. We report here that the expression of CD3{zeta} is significantly decreased in T cells infiltrating the SMs of patients with OA. The CD3{zeta} chain is involved in the T-cell signal transduction cascade, which is initiated by the engagement of the T-cell antigen receptor and which culminates in T-cell activation. Double immunofluorescence of single-cell suspensions derived from the SMs from nine patients with OA revealed significantly increased proportions of CD3{varepsilon}-positive (CD3{varepsilon}+) cells compared with the proportions of CD3{zeta}-positive (CD3{zeta}+) T cells (means ± standard errors of the means, 80.48% ± 3.92% and 69.02% ± 6.51%, respectively; P = 0.0096), whereas there were no differences in the proportions of these cells in peripheral blood mononuclear cells (PBMCs) from healthy donors (94.73% ± 1.39% and 93.79% ± 1.08%, respectively; not significant). The CD3{zeta}+ cell/CD3{varepsilon}+ cell ratio was also significantly decreased for T cells from the SMs of patients with OA compared with that for T cells from the PBMCs of healthy donors (0.84 ± 0.17 and 0.99 ± 0.01, respectively; P = 0.0302). The proportions of CD3{varepsilon}+ CD3{zeta}+ cells were lower in the SMs of patients with OA than in the PBMCs of healthy donors (65.04% ± 6.7% and 90.81% ± 1.99%, respectively; P = 0.0047). Substantial proportions (about 15%) of CD3{varepsilon}+ CD3{zeta}-negative (CD3{zeta}-) and CD3{varepsilon}-negative (CD3{varepsilon}-) CD3{zeta}- cells were found in the SMs of patients with OA. Amplification of the CD3{zeta} and CD3{delta} transcripts from the SMs of patients with OA by reverse transcriptase PCR consistently exhibited stronger bands for CD3{delta} cDNA than for CD3{zeta} cDNA The CD3{zeta}/CD3{delta} transcript ratio in the SMs of patients with OA was significantly lower than that in PBMCs from healthy controls (P < 0.0001). These results were confirmed by competitive MIMIC PCR. Immunoreactivities for the CD3{zeta} protein were detected in the SMs of 10 of 19 patients with OA, and they were of various intensities, whereas SMs from all patients were CD3{varepsilon}+ (P = 0.0023). The decreased expression of the CD3{zeta} transcript and protein in T cells from the SMs of patients with OA relative to that of the CD3{varepsilon} transcript is suggestive of chronic T-cell stimulation and supports the concept of T-cell involvement in OA.


* Corresponding author. Mailing address: Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA 19140. Phone: (215) 707-7929. Fax: (215) 707-7788. E-mail: chris.platsoucas{at}temple.edu.

{dagger} Present address: University of Thessaly, School of Medicine, Larisa 41222, Greece.


Clinical and Diagnostic Laboratory Immunology, January 2004, p. 195-202, Vol. 11, No. 1
1071-412X/04/$08.00+0     DOI: 10.1128/CDLI.11.1.195-202.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.