Characterization of T-cell repertoire of the bone marrow in immune-mediated aplastic anemia: evidence for the involvement of antigen-driven T-cell response in cyclosporine-dependent aplastic anemia.
Characterization of T-cell repertoire of the bone marrow in immune-mediated aplastic anemia: evidence for the involvement of antigen-driven T-cell response in cyclosporine-dependent aplastic anemia.
复制标题
免疫介导的再生障碍性贫血中骨髓 T 细胞库的表征：抗原驱动的 T 细胞反应参与环孢菌素依赖性再生障碍性贫血的证据。
作者：
W. Zeng;S. Nakao;H. Takamatsu;A. Yachie;A. Takami;Y. Kondo;N. Sugimori;H. Yamazaki;Yuji Miura;S. Shiobara;T. Matsuda
为了确定抗原驱动的T细胞应答是否参与再生障碍性贫血（AA）的发病机制，我们检测了未治疗的AA患者骨髓（BM）中T细胞受体（TCR）β链（BV）亚家族的互补决定区3（CDR 3）大小分布。免疫抑制治疗无效的AA患者和环孢霉素（CyA）或抗胸腺细胞球蛋白（ATG）治疗后早期获得未维持缓解的患者基本上表现出正常的CDR3大小模式。相比之下，5例需要持续给予CyA以维持缓解的患者在许多（>40%）BV亚家族中表现出偏斜的CDR3大小模式，提示克隆优势。CDR3大小分布的偏斜在CyA依赖性患者中变得不那么明显，当患者在4年CyA治疗后达到未维持的缓解时，而在另一个需要维持治疗的患者中持续超过7年。BV15 cDNA的测序显示，在所有CyA依赖性患者中，CDR 3大小模式表现出明显的克隆优势，这表明两个不同患者之间的CDR 3的氨基酸序列具有高度同源性。这些发现表明，抗原驱动的T细胞扩增参与AA的发病机制，其特征在于CyA依赖性造血恢复。
To determine whether the antigen-driven T-cell response is involved in the pathogenesis of aplastic anemia (AA), we examined the complementarity-determining region 3 (CDR3) size distribution of T-cell receptor (TCR) beta-chain (BV) subfamilies in the bone marrow (BM) of untreated AA patients. AA patients who did not respond to immunosuppressive therapy and those who obtained unmaintained remission early after cyclosporine (CyA) or antithymocyte globulin (ATG) therapy exhibited essentially a normal CDR3 size pattern. In contrast, five patients who needed continuous administration of CyA to maintain remission exhibited a skewed CDR3 size pattern in a number (>40%) of BV subfamilies suggestive of clonal predominance. The skewing of CDR3 size distribution became less pronounced in one of the CyA-dependent patients when the patient achieved unmaintained remission after a 4-year therapy with CyA, whereas it persisted longer than 7 years in the other patient requiring maintenance therapy. Sequencing of BV15 cDNA for which the CDR3 size pattern exhibited apparent clonal predominance in all CyA-dependent patients showed high homology of the amino acid sequence of the CDR3 between two different patients. These findings indicate that antigen-driven expansion of T cells is involved in the pathogenesis of AA characterized by CyA-dependent recovery of hematopoiesis.
影响因子：
15.9
作者：
FORMAN, JD;KLEIN, JT;MOLLER, DR
通讯作者：
MOLLER, DR
寡克隆类风湿关节炎滑膜 T 细胞共有 CDR3 序列基序。
DOI：
10.1172/jci117624
发表时间：
1994
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Li,Y;Sun,GR;Tumang,JR;Crow,MK;Friedman,SM
通讯作者：
Friedman,SM