Van den Hove L E, Van Gool S W, Vandenberghe P, Boogaerts M A, Ceuppens J L
Laboratory of Experimental Immunology, Faculty of Medicine, Catholic University of Leuven, Belgium.
Leukemia. 1998 Oct;12(10):1573-82. doi: 10.1038/sj.leu.2401146.
Three-color flow cytometry immunophenotyping revealed significant increases of CD57+ and CD28- cells among both circulating CD4+ and CD8+ T lymphocytes of untreated hemato-oncological patients (n = 54) as compared to healthy donors (n = 55), with CD57 and CD28 expression on the patients' T cells being largely reciprocal. Marked expansion of CD57+ cells among circulating CD4+ T lymphocytes was frequently detected in patients with chronic leukemia of B cell origin (B-CLL, hairy cell leukemia) but not in patients with chronic myeloid leukemia, suggesting a causal relation with the tumor's major histocompatibility complex class II expression. Using immunomagnetic separation techniques, we further demonstrate that the patients' CD57+/CD28- T cells display a typical Th1-type cytokine secretion profile upon anti-CD3 stimulation, with a markedly higher secretion of the Th1-type cytokines IL-2, IFN-gamma, and TNF-alpha than their CD57-/CD28+ counterparts. Cytotoxic activity of circulating CD8+ T lymphocytes, measured ex vivo in an anti-CD3-redirected assay, was almost exclusively exerted by the CD57+/CD28- subset. Moreover, a marked cytotoxic activity was detected within CD4+CD57+ T cells from some B-CLL patients. Finally, the patients' CD57+/CD28- T cells displayed an increased tendency to apoptosis in culture. Collectively, our results indicate that the expanded CD57+/CD28- T cells in hemato-oncological patients represent differentiated effector cells, similar to their (quantitatively minor) counterpart in healthy donors. The reason for their expansion and their pathophysiologic significance, however, remains unclear.
三色流式细胞术免疫表型分析显示，与健康供者（n = 55）相比，未经治疗的血液肿瘤患者（n = 54）循环CD4⁺和CD8⁺T淋巴细胞中CD57⁺和CD28⁻细胞显著增加，患者T细胞上的CD57和CD28表达在很大程度上呈负相关。在B细胞起源的慢性白血病（B-CLL、毛细胞白血病）患者中经常检测到循环CD4⁺T淋巴细胞中CD57⁺细胞的显著扩增，但在慢性髓性白血病患者中未检测到，这表明与肿瘤的主要组织相容性复合体II类表达存在因果关系。使用免疫磁珠分离技术，我们进一步证明，患者的CD57⁺/CD28⁻T细胞在抗CD3刺激后显示出典型的Th1型细胞因子分泌谱，其Th1型细胞因子IL-2、IFN-γ和TNF-α的分泌明显高于其CD57⁻/CD28⁺对应细胞。在抗CD3重定向试验中离体测量的循环CD8⁺T淋巴细胞的细胞毒性活性几乎完全由CD57⁺/CD28⁻亚群发挥。此外，在一些B-CLL患者的CD4⁺CD57⁺T细胞中检测到显著的细胞毒性活性。最后，患者的CD57⁺/CD28⁻T细胞在培养中显示出增加的凋亡倾向。总体而言，我们的结果表明，血液肿瘤患者中扩增的CD57⁺/CD28⁻T细胞代表分化的效应细胞，类似于健康供者中（数量较少）的对应细胞。然而，它们扩增的原因及其病理生理意义仍不清楚。
