Neubauer M A, Benyunes M C, Thompson J A, Bensinger W I, Lindgren C G, Buckner C D, Fefer A
Division of Oncology, University of Washington, Seattle 98195.
Bone Marrow Transplant. 1994 Mar;13(3):311-6.
Immunotherapy with interleukin-2 (IL-2) early after peripheral blood stem cell transplantation (PBSCT) is being considered as a potential way to eradicate minimal residual disease. The aim of this study was to determine whether lymphocytes which can acquire lymphokine-activated killer (LAK) cell activity are present in PBSC and in the blood of patients after PBSCT. Fresh and cryopreserved G-CSF-mobilized PBSC from eight patients were incubated with IL-2 (1000 U/ml) for 3-6 days and then tested for LAK activity as measured by lysis of the Daudi cell line. LAK activity was present in both fresh and cryopreserved PBSC, with mean lysis of 32% and 36%, respectively, at an effector:target (E:T) ratio of 50:1. To assess the reconstitution of LAK precursor activity after PBSCT, peripheral blood (PB) obtained from eight other patients 15-60 days after PBSCT was similarly tested. LAK activity was detected in PB from every patient (mean lysis of 38% at an E:T ratio of 12.5:1). PB from patients after PBSCT contained a higher percentage of CD8+ cells and CD56+ cells than did PB from 9 normal controls (47.2% vs. 21.4% CD8+ cells, P < 0.005 and 28.6% vs. 8.6% CD56+ cells, P < 0.0005). Moreover, PB from 4 of 5 patients tested after PBSCT exhibited a high percentage of cells expressing p75, the intermediate affinity IL-2R. Thus, precursor cells capable of acquiring IL-2-inducible LAK activity are present in PBSC and are rapidly reconstituted after PBSCT. The findings provide a rationale for testing IL-2 as a way of decreasing relapses after PBSCT.
外周血干细胞移植(PBSCT)后早期使用白细胞介素-2(IL-2)进行免疫治疗被认为是根除微小残留病的一种潜在方法。本研究的目的是确定在PBSC以及PBSCT后患者的血液中是否存在能够获得淋巴因子激活的杀伤细胞(LAK)活性的淋巴细胞。将来自8名患者的新鲜和冷冻保存的G-CSF动员的PBSC与IL-2(1000 U/ml)孵育3 - 6天,然后通过对Daudi细胞系的裂解来检测LAK活性。新鲜和冷冻保存的PBSC均具有LAK活性,在效应细胞与靶细胞(E:T)比例为50:1时,平均裂解率分别为32%和36%。为了评估PBSCT后LAK前体细胞活性的重建情况,对另外8名患者在PBSCT后15 - 60天获得的外周血(PB)进行了类似检测。在每位患者的PB中均检测到LAK活性(在E:T比例为12.5:1时,平均裂解率为38%)。PBSCT后患者的PB中CD8+细胞和CD56+细胞的百分比高于9名正常对照者的PB(CD8+细胞分别为47.2%对21.4%,P < 0.005;CD56+细胞分别为28.6%对8.6%,P < 0.0005)。此外,在PBSCT后检测的5名患者中的4名患者的PB中,表达p75(中等亲和力IL-2R)的细胞百分比很高。因此,能够获得IL-2诱导的LAK活性的前体细胞存在于PBSC中,并且在PBSCT后迅速重建。这些发现为将IL-2作为降低PBSCT后复发率的一种方法进行检测提供了理论依据。