Thomas R, McIlraith M, Davis L S, Lipsky P E
Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical School, Dallas 75235-8884.
Arthritis Rheum. 1992 Dec;35(12):1455-65. doi: 10.1002/art.1780351209.
To delineate the phenotype and function of synovial T cells in rheumatoid arthritis (RA).
T cells from normal subjects or from RA peripheral blood (PB), synovial fluid (SF), or synovial tissue (ST) were analyzed phenotypically and functionally.
RA SF and ST T cells were found to be markedly enriched in CD45RAdim, CD45RO+, CD45RBdim mature memory cells, whereas in the PB, CD45RAbright naive T cells were more frequent than CD45RO+ memory T cells, and only a minority were CD45RBdim. SF and ST T cells proliferated less well and produced less interleukin-2 in response to mitogenic stimuli than did PB T cells. However, synovial T cells effectively promoted the production of Ig from normal B cells. Moreover, PB and synovial T cells differed in their capacity to down-regulate immunoglobulin production. Anti-CD3-stimulated PB T cells suppressed Ig production unless their proliferation was prevented with mitomycin C. In contrast, synovial T cells were potent helpers of B cell Ig production regardless of antecedent treatment with mitomycin C. To examine the relationship between the CD45RBdim phenotype and B cell help, CD45RBdim T cells were sorted from PB. As opposed to the findings with synovial T cells, suppression by control PB CD45RBdim T cells was observed, but only when large numbers were employed. B cell Ig production was enhanced after treatment of PB CD45RBdim T cells with mitomycin C. In contrast, healthy control sorted CD45RBbright or sorted CD4+, CD45RO+, CD45RBbright T cells did not support Ig secretion. After treatment with mitomycin C, both of these populations were more effective helpers of Ig production.
RA synovium is enriched in differentiated CD45RBdim memory T cells with potent helper activity and diminished capacity to down-regulate B cells, strongly implying an active role for these cells in the production of Ig in the synovium, and thus in the propagation of disease.
明确类风湿关节炎（RA）中滑膜T细胞的表型和功能。
对来自正常受试者或RA外周血（PB）、滑液（SF）或滑膜组织（ST）的T细胞进行表型和功能分析。
发现RA SF和ST T细胞中CD45RAdim、CD45RO+、CD45RBdim成熟记忆细胞显著富集，而在PB中，CD45RAbright初始T细胞比CD45RO+记忆T细胞更常见，且只有少数是CD45RBdim。与PB T细胞相比，SF和ST T细胞对有丝分裂原刺激的增殖能力较差，产生的白细胞介素-2也较少。然而，滑膜T细胞能有效促进正常B细胞产生Ig。此外，PB和滑膜T细胞下调免疫球蛋白产生的能力不同。抗CD3刺激的PB T细胞抑制Ig产生，除非用丝裂霉素C阻止其增殖。相反，滑膜T细胞无论是否先用丝裂霉素C处理，都是B细胞Ig产生的有效辅助细胞。为了研究CD45RBdim表型与B细胞辅助之间的关系，从PB中分选CD45RBdim T细胞。与滑膜T细胞的结果相反，对照PB CD45RBdim T细胞观察到有抑制作用，但只有在使用大量细胞时才会出现。用丝裂霉素C处理PB CD45RBdim T细胞后，B细胞Ig产生增强。相反，健康对照分选的CD45RBbright或分选的CD4+、CD45RO+、CD45RBbright T细胞不支持Ig分泌。用丝裂霉素C处理后，这两个群体都是Ig产生更有效的辅助细胞。
RA滑膜中富含具有强大辅助活性且下调B细胞能力减弱的分化型CD45RBdim记忆T细胞，强烈提示这些细胞在滑膜中Ig产生以及疾病传播中发挥积极作用。
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