Clonal expansion within the CD4+CD57+ and CD8+CD57+ T cell subsets in chronic lymphocytic leukemia.
Clonal expansion within the CD4+CD57+ and CD8+CD57+ T cell subsets in chronic lymphocytic leukemia.
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DOI：
10.4049/jimmunol.158.3.1482
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发表时间：
1997-02
影响因子：
4.4
通讯作者：
D. Serrano;J. Monteiro;S. L. Allen;J. Kolitz;P. Schulman;S. Lichtman;A. Buchbinder;V. Vinciguerra;N. Chiorazzi;P. Gregersen
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文献类型：
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作者：
D. Serrano;J. Monteiro;S. L. Allen;J. Kolitz;P. Schulman;S. Lichtman;A. Buchbinder;V. Vinciguerra;N. Chiorazzi;P. Gregersen
T细胞在慢性淋巴细胞白血病（CLL）中的作用尚未得到广泛研究，因为CLL中最突出的细胞异常涉及B细胞的克隆扩增。在这项研究中，我们对CLL患者（n = 19）和年龄匹配的对照组（n = 22）中的CD 4+和CD 8 + T细胞库进行了全面分析。使用针对CDR 3长度的多重PCR测定进行TCR库分析，该方法允许检测复杂T细胞群体中潜在的寡克隆性。我们确定，CLL患者的CD 4+和CD 8 + T细胞群中寡克隆性显著高于年龄匹配的对照组（p < 0.001）。使用一组TCRV片段特异性mAb进行三色FACS分析，我们还确定寡克隆扩增主要见于CD 4+和CD 8 + T细胞群的CD 57+亚群中。与正常对照组（%CD 57 = 3.3 +/- 3.0%; p < 0.001）相比，CLL组（%CD 57 = 14.8 +/- 13.0%）中CD 4 + T细胞上CD 57标记物的频率增加。CD 4 + CD 57 + T细胞的频率升高与更晚期的疾病相关。类似地，CD 4 + CD 57 + T细胞的最极端寡克隆扩增发生在已经进展超过Rai 0期的CLL患者中。这些数据记录了CLL患者T细胞库的深刻变化，并指出克隆T细胞群在这种疾病的发病机制中的作用。
The role of T cells in chronic lymphocytic leukemia (CLL) has not been extensively investigated, since the most prominent cellular abnormality in CLL involves the clonal expansion of B cells. In this study we have undertaken a comprehensive analysis of the CD4+ and CD8+ T cell repertoire in a population of CLL patients (n = 19) and age-matched controls (n = 22). The TCR repertoire analysis was performed using a multiplex PCR assay for CDR3 length, an approach that allows for the detection of underlying oligoclonality in complex T cell populations. We established that oligoclonality was substantially more frequent in both the CD4+ and CD8+ T cell populations of CLL patients than in the age-matched controls (p < 0.001). Using three-color FACS analysis with a panel of TCRV segment-specific mAbs, we also established that oligoclonal expansions are predominantly found in the CD57+ subset of both the CD4+ and CD8+ T cell populations. The frequency of the CD57 marker on CD4+ T cells was increased in the setting of CLL (% CD57 = 14.8 +/- 13.0%) compared with that in normal controls (% CD57 = 3.3 +/- 3.0%; p < 0.001). An elevated frequency of CD4+CD57+ T cells was correlated with more advanced disease. Similarly, the most extreme oligoclonal expansions of CD4+CD57+ T cells occurred in CLL patients who had progressed beyond Rai stage 0. These data document profound alterations in the T cell repertoire of CLL patients and point to a role for clonal T cell populations in the pathogenesis of this disease.