HLA-DR-EXPRESSING CD8BRIGHT CELLS ARE ONLY TEMPORARILY PRESENT IN THE CIRCULATION DURING SUBCUTANEOUS RECOMBINANT INTERLEUKIN-2 THERAPY IN RENAL-CELL CARCINOMA PATIENTS
HLA-DR-EXPRESSING CD8BRIGHT CELLS ARE ONLY TEMPORARILY PRESENT IN THE CIRCULATION DURING SUBCUTANEOUS RECOMBINANT INTERLEUKIN-2 THERAPY IN RENAL-CELL CARCINOMA PATIENTS
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DOI：
10.1007/bf01741092
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发表时间：
1993-03-01
影响因子：
5.8
通讯作者：
DELEIJ, L
中科院分区：
文献类型：
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作者：
JANSSEN, RAJ;BUTER, J;DELEIJ, L
一项纵向研究调查了皮下重组白细胞介素 2 (rIL-2) 疗法对 17 名肾细胞癌患者外周血淋巴细胞 (PBL)“激活状态”的影响。使用全血样本的双色流式细胞术分析细胞毒性 T 细胞、辅助 T 细胞和自然杀伤 (NK) 细胞上激活标记 HLA-Dr 和 CD25 的表达。此外，还研究了分离的 PBL 响应各种刺激的体外增殖能力。在整个治疗过程中，NK细胞和表达HLA-DR的NK细胞的绝对量持续增加。然而，T 细胞和表达 HLA-Dr 的 T 细胞的绝对量仅在治疗的前 1 或 2 周内显示出早期增加，此后表达 HLA-Dr 的 T 细胞的绝对量下降。特别是，在治疗的后半段，表达HLA-Dr的CD8bright+-T细胞的绝对量显着降低。治疗第 7 天收集的 PBL（第一周期后 PBL）显示，与治疗前收集的 PBL（治疗前 PBL）相比，用植物血凝素、刀豆球蛋白 A、可溶性 CD3 mAb (WT32) 或 rIL-2 刺激后，体外增殖反应降低。周期 1 后 PBL 的体外反应降低也反映在 rIL-2 或 CD3 mAb 培养物中表达 HLA-Dr 的 CD8bright+ T 细胞百分比下降，而治疗前 PBL 培养物则显示该百分比有所增加。我们得出结论，在皮下 rIL-2 治疗的前 2 周内，T 细胞是主要受刺激的亚群。治疗后半期外周血中表达 HLA-Dr 的 T 细胞绝对量显着减少，部分原因可能是对 rIL-2 的反应性降低，但也可能涉及表达 HLA-Dr 的细胞的选择性重新分布。
The effect of subcutaneous recombinant interleukin-2 (rIL-2) therapy on the ''activation status'' of peripheral blood lymphocytes (PBL) of 17 renal cell carcinoma patients was investigated in a longitudinal study. The expression of the activation markers HLA-Dr and CD25 on cytotoxic T cells, helper T cells, and natural killer (NK) cells, was analysed using two-colour flow cytometry of whole-blood samples. In addition, the ability of isolated PBL to proliferate in vitro in response to various stimuli was investigated. The absolute amounts of NK cells and HLA-DR-expressing NK cells increased continuously during the whole course of therapy. The absolute amounts of T cells and HLA-Dr-expressing T cells, however, showed an early increase only during the first 1 or 2 weeks of therapy, after which the absolute amounts of HLA-Dr-expressing T cells decreased. In particular, the absolute amount of HLA-Dr-expressing CD8bright+- T cells was significantly lowered in the second half of therapy. PBL collected on day 7 of therapy (post-cycle-I PBL) showed, as compared to those collected prior to therapy (pretherapy PBL), a decreased proliferative response in vitro after stimulation with phytohaemagglutinin, concanavalin A, soluble CD3 mAb (WT32) or rIL-2. This decreased in vitro response of post-cycle-1 PBL was also reflected in a decrease in the percentage of CD8bright+ T cells expressing HLA-Dr in cultures with rIL-2 or CD3 mAb, in contrast to cultures of pretherapy PBL, which showed an increase of this percentage. We conclude that T cells are the predominantly stimulated subpopulation during the first 2 weeks of subcutaneous rIL-2 therapy. The significant decrease in the absolute amounts of HLA-Dr-expressing T cells in the peripheral blood during the second half of therapy may partly be explained by a decreased responsiveness to rIL-2, but a selective redistribution of HLA-Dr-expressing cells may also be involved.