Kuss Iris, Schaefer Carsten, Godfrey Tony E, Ferris Robert L, Harris Jeffrey M, Gooding William, Whiteside Theresa L
University of Pittsburgh Cancer Institute, PA 15213-1863, USA.
Clin Immunol. 2005 Jul;116(1):27-36. doi: 10.1016/j.clim.2004.12.011.
Apoptosis of circulating CD8+ T lymphocytes is a frequent finding in patients with cancer. T-cell output by the thymus or antigen-driven expansion of circulating T cells could compensate for apoptosis and thus normalize their homeostasis. We studied the frequency of recent thymic emigrants (RTE) identified by T-cell receptor excision circles (TREC) and of naive and memory T-cell subsets in peripheral blood samples obtained from 39 patients with head and neck cancer (HNC) and 33 age-matched controls (NC). TREC numbers were determined by real-time quantitative PCR, and CD8+CD45RO-CD27+ or CD4+CD45RO-CD27+ T-cell subsets were quantified by flow cytometry. Age-associated decreases in TREC numbers and proportions of naive CD8+ and CD4+ T-cell subsets were significantly greater in cancer patients than NC. In contrast, the memory compartment was expanded, with increased proportions of CD4+CD45RO+ but not CD8+CD45RO+ T cells, in cancer patients vs. NC. These alterations did not normalize in patients who were NED. The data suggest that lower thymic output combined with rapid turnover of naive CD8+ T cells account for altered lymphocyte homeostasis in HNC patients. The defect persists long after curative treatments and may contribute to immune cell dysregulation in patients with cancer.
循环CD8⁺ T淋巴细胞凋亡在癌症患者中很常见。胸腺输出的T细胞或循环T细胞的抗原驱动扩增可以补偿细胞凋亡，从而使其稳态正常化。我们研究了通过T细胞受体切除环（TREC）鉴定的近期胸腺迁出者（RTE）以及从39例头颈癌（HNC）患者和33例年龄匹配的对照（NC）获得的外周血样本中幼稚和记忆T细胞亚群的频率。通过实时定量PCR确定TREC数量，并通过流式细胞术对CD8⁺CD45RO⁻CD27⁺或CD4⁺CD45RO⁻CD27⁺ T细胞亚群进行定量。与年龄相关的TREC数量减少以及幼稚CD8⁺和CD4⁺ T细胞亚群比例的下降在癌症患者中比NC组明显更大。相反，与NC组相比，癌症患者的记忆细胞区室扩大，CD4⁺CD45RO⁺ T细胞比例增加，但CD8⁺CD45RO⁺ T细胞比例未增加。这些改变在无疾病证据（NED）的患者中并未恢复正常。数据表明，较低的胸腺输出量与幼稚CD8⁺ T细胞的快速更新共同导致了HNC患者淋巴细胞稳态的改变。这种缺陷在根治性治疗后很长时间仍然存在，可能导致癌症患者免疫细胞失调。
