Tötterman T H, Carlsson M, Simonsson B, Bengtsson M, Nilsson K
Department of Clinical Immunology & Transfusion Medicine, University Hospital, Uppsala, Sweden.
Blood. 1989 Aug 1;74(2):786-92.
Two-color FACS analysis was used to study activated and "functional" T and natural killer (NK) cell subsets of circulating lymphocytes in 23 patients with B-type chronic lymphocytic leukemia (B-CLL) and in 30 healthy subjects. As compared with controls, B-CLL patients had increased absolute numbers of phenotypically activated, HLA-DR+ CD4+ and CD8+ cells and T suppressor/effector (CD11b+CD8+) cells. When patients in Rai stages II through IV (n = 11) were compared with cases in Rai stages O through I (n = 12), the former group of patients had higher numbers of activated CD4+ and CD8+ T cells and decreased levels of suppressor/effector T cells. The absolute numbers of T suppressor/inducer (CD45R+CD4+) cells were elevated in patients with stage O through I disease but within normal range in stage II through IV leukemia. We further showed that the absolute numbers of NK-like (CD16+) cells and their activated counterparts (DR+CD16+) are elevated in B-CLL patients as compared with healthy subjects. The comparison of relative T and NK subsets in the blood of patients and controls showed that the proportions of CD4+, CD8+, and CD16+ cells expressing the activation marker HLA-DR were increased in B-CLL. Furthermore, the percentage of T-suppressor/inducer (CD45R+) cells within the CD4+ population was decreased in the patients. The proportion of T-suppressor/effector (CD11b+) cells within the CD8+ subset was reduced in subjects with stage II-IV disease only. When stimulated in vitro with the T-cell-dependent inducer TPA, B-CLL cells from patients in Rai stages II through IV secreted larger amounts of IgM as compared with cells from stage O through I patients. A positive correlation was observed between the degree of phenotypic activation of CD4+ T-helper cells and their functional capacity to augment IgM secretion by autologous B-CLL cells. Our findings indicate a tumor cell-directed regulatory role of T cells (and possibly NK cells as well) in B-CLL. Furthermore, monitoring of phenotypically activated and functional T-cell subsets may be helpful in the prediction of disease progression and timing of therapy in B-CLL.
采用双色荧光激活细胞分选术（FACS）分析了23例B型慢性淋巴细胞白血病（B-CLL）患者及30名健康受试者循环淋巴细胞中活化的及“功能性”T细胞和自然杀伤（NK）细胞亚群。与对照组相比，B-CLL患者表型活化的、HLA-DR+ CD4+和CD8+细胞以及T抑制/效应细胞（CD11b+CD8+）的绝对数量增加。将Rai分期II至IV期的患者（n = 11）与Rai分期0至I期的患者（n = 12）进行比较，前一组患者活化的CD4+和CD8+ T细胞数量更多，而抑制/效应T细胞水平降低。Rai分期0至I期疾病患者的T抑制/诱导细胞（CD45R+CD4+）绝对数量升高，但在II至IV期白血病患者中处于正常范围。我们进一步发现，与健康受试者相比，B-CLL患者中NK样细胞（CD16+）及其活化对应物（DR+CD16+）的绝对数量升高。对患者和对照者血液中相对T细胞和NK细胞亚群的比较显示，B-CLL患者中表达活化标志物HLA-DR的CD4+、CD8+和CD16+细胞比例增加。此外，患者中CD4+群体内T抑制/诱导细胞（CD45R+）的百分比降低。仅在II-IV期疾病受试者中，CD8+亚群内T抑制/效应细胞（CD11b+）的比例降低。当用T细胞依赖性诱导剂佛波酯（TPA）体外刺激时，Rai分期II至IV期患者的B-CLL细胞比0至I期患者的细胞分泌更多的IgM。观察到CD4+辅助性T细胞的表型活化程度与其增强自体B-CLL细胞IgM分泌的功能能力之间存在正相关。我们的研究结果表明T细胞（可能还有NK细胞）在B-CLL中具有针对肿瘤细胞的调节作用。此外，监测表型活化和功能性T细胞亚群可能有助于预测B-CLL的疾病进展和治疗时机。
