Clonal V alpha 12.1+ T cell expansions in the peripheral blood of rheumatoid arthritis patients.
Clonal V alpha 12.1+ T cell expansions in the peripheral blood of rheumatoid arthritis patients.
复制标题
克隆vα12.1+ T细胞在类风湿关节炎患者外周血中的扩张。
DOI：
10.1084/jem.177.6.1623
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发表时间：
1993-06-01
期刊：
影响因子：
--
通讯作者：
Brenner MB
中科院分区：
文献类型：
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作者：
DerSimonian H;Sugita M;Glass DN;Maier AL;Weinblatt ME;Rème T;Brenner MB
类风湿性关节炎（RA）是一种以慢性多发性关节炎为特征的异质性疾病。大多数成人RA患者遗传HLA-DR4或-DR1主要组织相容性复合体（MHC）基因。虽然这种遗传倾向的分子基础尚不清楚，但这些mhc编码分子的主要功能是向T淋巴细胞提供肽。据推测，内源性或环境抗原启动由T淋巴细胞介导的mhc限制性免疫反应，随后是涉及多种细胞类型的慢性炎症反应。在慢性RA中，先前或正在进行的抗原激活可能导致外周α / β T细胞受体（TCR）库可检测到的倾斜。本研究显示，约15%的RA患者外周血中携带V α 12.1的CD8+ T细胞显著扩增（平均22%，范围10-43%）。除了预期的高频率DR1和DR4等位基因外，这些患者中有很大一部分共享HLA-DQ2。对3例V α 12.1+ T细胞升高的RA患者进行详细的分子分析，发现重复的TCR α链序列与克隆V α 12.1+、CD8+ T细胞扩增一致。除了在不相关的受试者中共享TCR V α 12.1种系基因外，还检测到保守的J α基序。总之，这些结果提示了抗原驱动的T细胞在这些患者中扩增的机制，并可能提供一种新的方法来检测刺激RA中T细胞的特异性抗原。
Rheumatoid arthritis (RA) represents a heterogenous disease characterized by chronic polyarthritis. Most patients with adult RA inherit HLA-DR4 or -DR1 major histocompatibility complex (MHC) genes. While the molecular basis for this genetic predisposition is unknown, the major function of these MHC-encoded molecules is to present peptides to T lymphocytes. It is hypothesized that an endogenous or environmental antigen initiates a MHC-restricted immune response mediated by T lymphocytes, which is followed by a chronic inflammatory reaction involving many cell types. In chronic RA, previous or ongoing antigenic activation might result in detectable skewing of the peripheral alpha/beta T cell receptor (TCR) repertoire. Here we demonstrate a marked expansion of V alpha 12.1-bearing CD8+ T cells in the peripheral blood (mean, 22%; range, 10-43%) of > 15% of RA patients. A major proportion of these patients shared HLA-DQ2 in addition to the expected high frequency DR1 and DR4 alleles. Detailed molecular analysis in three of the RA patients with elevated V alpha 12.1+ T cells identified repeated TCR alpha chain sequences consistent with clonal V alpha 12.1+,CD8+ T cell expansion. In addition to shared TCR V alpha 12.1 germline gene usage among unrelated subjects, a conserved J alpha motif was also detected. Together, these results suggest an antigen-driven mechanism of T cell expansion in these patients and may offer a new approach in examining specific antigen that stimulate T cells in RA.