Singh R K, Varney M L, Buyukberber S, Ino K, Ageitos A G, Reed E, Tarantolo S, Talmadge J E
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha 68198-5660, USA.
Cancer Res. 1999 Jul 1;59(13):3107-11.
We report the preferential expression of Fas on CD4+ T cells and Fas ligand (FasL) on monocytes and their potential role in the selective loss of CD4+ T cells in breast cancer patients undergoing high-dose chemotherapy and peripheral blood stem cell transplantation (PSCT). A high frequency of apoptotic CD4+ T cells (28-51%) is observed during the first 100 days after PSCT concomitant with a significant increase in monocyte frequency and FasL expression (11.6-23%) on monocytes. The preferential expression of Fas on CD4+ T cells (73-92%) in the peripheral blood (PB) of these patients is associated with a significantly higher frequency of CD4+ T-cell apoptosis compared with CD8+ T cells (28-47%) and CD4+ T cells (46 +/- 5.7%) in normal PB. These data suggest that "primed" Fas+ CD4+ lymphocytes interact with activated monocytes that express FasL, resulting in apoptosis, leading to deletion of CD4+ T cells, an inversion in the CD4:CD8 T-cell ratio, and immune dysfunction. The prevention of CD4+ T-cell apoptosis and improved immune reconstitution by the manipulation of PB stem cell products, blockade of Fas-FasL interactions, or cytokine support after transplantation may be important adjuvant immunotherapeutic strategies in patients undergoing high-dose chemotherapy and PSCT.
我们报告了Fas在CD4+ T细胞上的优先表达以及Fas配体（FasL）在单核细胞上的表达，及其在接受大剂量化疗和外周血干细胞移植（PSCT）的乳腺癌患者CD4+ T细胞选择性丢失中的潜在作用。在PSCT后的前100天内观察到高频率的凋亡CD4+ T细胞（28%-51%），同时单核细胞频率和单核细胞上FasL表达（11.6%-23%）显著增加。与正常外周血（PB）中的CD8+ T细胞（28%-47%）和CD4+ T细胞（46±5.7%）相比，这些患者外周血（PB）中CD4+ T细胞上Fas的优先表达（73%-92%）与CD4+ T细胞凋亡频率显著更高有关。这些数据表明，“致敏的”Fas+ CD4+淋巴细胞与表达FasL的活化单核细胞相互作用，导致细胞凋亡，从而导致CD4+ T细胞缺失、CD4:CD8 T细胞比值倒置和免疫功能障碍。通过对外周血干细胞产物进行处理、阻断Fas-FasL相互作用或移植后给予细胞因子支持来预防CD4+ T细胞凋亡和改善免疫重建，可能是接受大剂量化疗和PSCT患者重要的辅助免疫治疗策略。
