Hank J A, Sosman J A, Kohler P C, Bechhofer R, Storer B, Sondel P M
Department of Human Oncology, University of Wisconsin, Madison.
J Biol Response Mod. 1990 Feb;9(1):5-14.
Peripheral blood lymphocytes obtained from cancer patients receiving interleukin-2 (IL-2) on two separate clinical protocols were evaluated for their in vitro responses to IL-2, alloantigens, and PHA. IL-2 in vivo induced enhanced in vitro proliferative responses to IL-2 and diminished in vitro proliferative responses to phytohemagglutinin (PHA) and alloantigens. Alloinduced cytotoxic T cell responses were also depressed following in vivo IL-2. We examined the kinetics of the in vitro proliferative response to PHA and IL-2 and found that while the response of lymphocytes primed in vivo with IL-2 to PHA was depressed at all times during the 2 week in vitro exposure, the response to IL-2 peaked earlier and higher than did the response to IL-2 by lymphocytes obtained prior to IL-2 therapy. These contrasting effects on antigen-induced T cell responses vs. IL-2 induced nonspecific proliferative and cytotoxic responses suggest the importance of dose and timing of IL-2 administration when used to enhance antigen-specific T cell responses or as an immune enhancing agent combined with vaccines.
对接受两种不同临床方案的白细胞介素-2（IL-2）治疗的癌症患者获取的外周血淋巴细胞，评估其对IL-2、同种异体抗原和PHA的体外反应。体内IL-2诱导对IL-2的体外增殖反应增强，而对植物血凝素（PHA）和同种异体抗原的体外增殖反应减弱。体内给予IL-2后，同种异体诱导的细胞毒性T细胞反应也受到抑制。我们研究了对PHA和IL-2的体外增殖反应动力学，发现虽然在体外暴露的2周内，体内用IL-2致敏的淋巴细胞对PHA的反应在任何时候都受到抑制，但对IL-2的反应比IL-2治疗前获取的淋巴细胞对IL-2的反应更早达到峰值且峰值更高。这些对抗原诱导的T细胞反应与IL-2诱导的非特异性增殖和细胞毒性反应的不同影响表明，当使用IL-2增强抗原特异性T细胞反应或作为与疫苗联合使用的免疫增强剂时，IL-2给药的剂量和时间很重要。
