Yamaga K M, Bolen H, Kimura L, Lance E M
Shriners Hospitals for Crippled Children, Honolulu, HI 96826.
Arthritis Rheum. 1993 Apr;36(4):500-13. doi: 10.1002/art.1780360410.
The lysis of chondrocytes, the parenchymal cells of cartilage, by lymphocytes may provide a potent mechanism by which the immune system participates in sustaining joint damage in rheumatoid arthritis (RA). We studied the capability of lymphocytes from healthy individuals and patients with arthritis to lyse chondrocytes.
Peripheral blood mononuclear cells (PMBC) were tested for their ability to lyse chondrocytes in a 51Cr-release assay. Enhancement of the chondrolytic activity was determined by preincubating the cells with T cell growth factor (TCGF) or recombinant interleukin-2 (rIL-2) before cytotoxic testing.
PBMC from healthy individuals possessed a low ability to lyse chondrocytes, whereas cells from the synovial fluid of patients with RA displayed higher chondrolytic activity. In RA, modulating factors must come into play because not all synovial fluid sample cells showed high chondrolytic activity and cells from synovial tissue had little or no lytic action on chondrocytes. Chondrolytic activities of cells from all sources, including PBMC from healthy subjects and patients with arthritis and cells isolated from synovial fluid or from the synovial tissue of RA patients, were greatly increased by incubating the cells with TCGF or rIL-2. In contrast, treatment of chondrocytes with interferon-gamma, which enhances major histocompatibility complex gene expression, decreased the susceptibility of chondrocytes to lysis.
These observations suggest a mechanism for joint damage in which the destruction of chondrocytes by lymphocytes is controlled by cytokines released during the inflammatory process in arthritic diseases.
淋巴细胞对软骨实质细胞软骨细胞的裂解可能提供一种有力的机制，通过该机制免疫系统参与类风湿性关节炎（RA）中关节损伤的持续过程。我们研究了健康个体和关节炎患者的淋巴细胞裂解软骨细胞的能力。
采用51Cr释放试验检测外周血单核细胞（PMBC）裂解软骨细胞的能力。在细胞毒性试验前，通过将细胞与T细胞生长因子（TCGF）或重组白细胞介素-2（rIL-2）预孵育来确定软骨溶解活性的增强情况。
健康个体的PBMC裂解软骨细胞的能力较低，而RA患者滑液中的细胞表现出较高的软骨溶解活性。在RA中，调节因子必定发挥了作用，因为并非所有滑液样本细胞都表现出高软骨溶解活性，并且滑膜组织中的细胞对软骨细胞几乎没有或没有裂解作用。通过将所有来源的细胞与TCGF或rIL-2孵育，包括健康受试者和关节炎患者的PBMC以及从RA患者的滑液或滑膜组织中分离的细胞，其软骨溶解活性大大增加。相比之下，用干扰素-γ处理软骨细胞，这会增强主要组织相容性复合体基因表达，降低了软骨细胞对裂解的敏感性。
这些观察结果提示了一种关节损伤机制，其中淋巴细胞对软骨细胞的破坏由关节炎疾病炎症过程中释放的细胞因子控制。
