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通过对未改变病毒学、免疫学或临床参数的HIV感染患者进行淋巴细胞分离术来恢复用于过继性免疫治疗的T淋巴细胞。

Recovery of T-lymphocytes for adoptive immunotherapy by lymphapheresis of HIV-infected patients without alterations of virological, immunological or clinical parameters.

作者信息

van Lunzen J, Schmitz J, Dengler K, Schmidt L, Schmitz H, Dietrich M

机构信息

Clinical Medicine Section, Bernhard-Nocht-Institute for Tropical Medicine, Hamburg, Germany.

出版信息

Br J Haematol. 1994 Sep;88(1):46-51. doi: 10.1111/j.1365-2141.1994.tb04975.x.

Abstract

We performed repeated continuous flow cytaphereses (CFC) on 13 asymptomatic HIV-1-infected patients to study the feasibility of cell separation procedures to recover high yields of peripheral blood T-lymphocytes for adoptive immunotherapy in HIV-infected patients and to determine immunological and virological alterations following such procedures. A mean yield of 6.23 x 10(9) lymphocytes could be obtained by each cytapheresis, containing 1.82 x 10(9) CD4+, 3.23 x 10(9) CD8+ T-lymphocytes and 8.39 x 10(6) CD34+ peripheral progenitor cells. The CD4/CD8 ratio (mean 0.53, SD +/- 0.15) in the cell samples reflected the distribution of the lymphocyte subsets in vivo. Absolute lymphocyte counts decreased at a mean of 404/mm3 (25%) immediately after CFC but were replaced from the extravascular pool within 1 h. The CD4/CD8 ratios, p24-antigenaemia, HLA-DR expression and neopterin levels did not change significantly after cell separation. No alteration of the number of T-cells with integrated proviral DNA copies (1/10(3) to 1/10(6)) could be detected in peripheral T-helper cells by PCR after lymphapheresis. We conclude that high yields of peripheral T-lymphocytes can be obtained by continuous flow lymphapheresis for cell-mediated immunotherapy, without deterioration of virological or immunological parameters in HIV-infected patients. The separated T-cells are fully replaced from extravascular pools after 1 h.

摘要

我们对13例无症状HIV-1感染患者进行了重复连续流式细胞分离术(CFC),以研究细胞分离程序在为HIV感染患者进行过继免疫治疗时回收高产率外周血T淋巴细胞的可行性,并确定此类程序后的免疫和病毒学改变。每次细胞分离术平均可获得6.23×10⁹个淋巴细胞,其中包含1.82×10⁹个CD4⁺、3.23×10⁹个CD8⁺T淋巴细胞和8.39×10⁶个CD34⁺外周祖细胞。细胞样本中的CD4/CD8比值(平均0.53,标准差±0.15)反映了体内淋巴细胞亚群的分布。CFC后即刻绝对淋巴细胞计数平均下降404/mm³(25%),但在1小时内从血管外池得到补充。细胞分离后CD4/CD8比值、p24抗原血症、HLA-DR表达和新蝶呤水平均无显著变化。通过聚合酶链反应(PCR)在淋巴细胞去除术后的外周辅助性T细胞中未检测到整合有前病毒DNA拷贝(1/10³至1/10⁶)的T细胞数量改变。我们得出结论,连续流式淋巴细胞去除术可为细胞介导的免疫治疗获得高产率外周T淋巴细胞,而不会使HIV感染患者的病毒学或免疫学参数恶化。分离的T细胞在1小时后从血管外池得到完全补充。

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