| Autor: |
Sakkas, Lazaros I., Koussidis, George, Avgerinos, Efthimios, Gaughan, John, Platsoucas, Chris D. |
| Zdroj: |
Clinical and Vaccine Immunology (formerly CDLI); January 2004, Vol. 11 Issue: 1 p195-202, 8p |
| Abstrakt: |
ABSTRACTOsteoarthritis (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? is significantly decreased in T cells infiltrating the SMs of patients with OA. The CD3? 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 CD3e-positive (CD3e+) cells compared with the proportions of CD3?-positive (CD3?+) 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?+cell/CD3e+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 CD3e+CD3?+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 CD3e+CD3?-negative (CD3?-) and CD3e-negative (CD3e-) CD3?-cells were found in the SMs of patients with OA. Amplification of the CD3? and CD3d transcripts from the SMs of patients with OA by reverse transcriptase PCR consistently exhibited stronger bands for CD3d cDNA than for CD3? cDNA The CD3?/CD3d 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? 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 CD3e+(P= 0.0023). The decreased expression of the CD3? transcript and protein in T cells from the SMs of patients with OA relative to that of the CD3e transcript is suggestive of chronic T-cell stimulation and supports the concept of T-cell involvement in OA. |
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