Cush J J, Pietschmann P, Oppenheimer-Marks N, Lipsky P E
Harold C. Simmons Arthritis Research Center, University of Texas Southwestern Medical Center, Dallas 75235.
Arthritis Rheum. 1992 Dec;35(12):1434-44. doi: 10.1002/art.1780351206.
Mechanisms controlling the infiltration of T cells into rheumatoid synovium have not been fully characterized. These studies were undertaken to investigate the relationship between T cell phenotype and migratory capacity, so as to elucidate mechanisms that might contribute to the accumulation of T cells at inflammatory sites.
The characteristics of in vivo migrating cells were studied by dual-immunofluorescence FACS (fluorescence-activated cell sorter) analysis of rheumatoid synovial and peripheral blood T cells. Migratory cells were also characterized using a recently developed in vitro assay, wherein peripheral blood T lymphocytes (PBTL) with the capacity to migrate through endothelial cell monolayers were retrieved and assessed.
Migratory CD4+ T cells from rheumatoid arthritis (RA) and normal individuals were characterized as being CD45RA-, CD29bright, CD11abright, L-selectin-, CD54+, and CD58+. Migrating RA PBTL (compared with normal PBTL), however, were significantly enriched in activated HLA-DR+ T cells. RA synovial tissue lymphocytes exhibited a similar phenotype, but with decreased surface density of CD4 and an increase in HLA-DR and VLA-1. RA synovial lymphocytes exhibited a 2-3-fold increase in migratory capacity over normal and RA PBTL:
These studies demonstrate the inherent migratory proficiency of CD4+ T cells that express a memory phenotype (CD29bright, CD11abright, and CD58+). In addition, enhanced transendothelial migration was observed for CD4+ T cells that were CD54+ and L-selectin-. These studies demonstrate that the migratory patterns of circulating lymphocytes may be correlated with their surface phenotype and that the intrinsic migratory capacity of memory T cells is one component contributing to their accumulation in the rheumatoid synovium.
控制T细胞浸润至类风湿性滑膜的机制尚未完全明确。开展这些研究以调查T细胞表型与迁移能力之间的关系，从而阐明可能导致T细胞在炎症部位积聚的机制。
通过对类风湿性滑膜和外周血T细胞进行双免疫荧光流式细胞术（荧光激活细胞分选仪）分析，研究体内迁移细胞的特征。还使用最近开发的体外试验对迁移细胞进行表征，其中检索并评估具有穿过内皮细胞单层迁移能力的外周血T淋巴细胞（PBTL）。
类风湿性关节炎（RA）患者和正常个体的迁移性CD4+ T细胞特征为CD45RA-、CD29bright、CD11abright、L-选择素-、CD54+和CD58+。然而，迁移的RA PBTL（与正常PBTL相比）中活化的HLA-DR+ T细胞显著富集。RA滑膜组织淋巴细胞表现出相似的表型，但CD4的表面密度降低，HLA-DR和VLA-1增加。RA滑膜淋巴细胞的迁移能力比正常和RA PBTL增加了2-3倍。
这些研究证明了表达记忆表型（CD29bright、CD11abright和CD58+）的CD4+ T细胞具有固有的迁移能力。此外，观察到CD54+和L-选择素-的CD4+ T细胞跨内皮迁移增强。这些研究表明循环淋巴细胞的迁移模式可能与其表面表型相关，并且记忆T细胞的内在迁移能力是其在类风湿性滑膜中积聚的一个因素。
