一项初步研究结果提示，重组人类白介素7（rhIL-7）可以增强因为淋巴细胞去除而免疫受损的患者的免疫反应。1期试验结果发表在6月23日的《实验医学杂志》上，研究表明在癌症患者中使用，rhIL-7可以诱导CD4+和CD8+T细胞明显的多克隆长期扩增，最终导致明显的循环T细胞受体库多样性增加。这些影响是通过增加外周血T细胞循环和细胞存活机制产生。
细胞毒性化疗引起的淋巴细胞减少或者HIV感染病理学，都可以明显减弱免疫功能，作为生理性免疫增强剂，IL-7可以增强T细胞恢复。有严重缺乏的成人中CD4+T细胞恢复需要初始T细胞库再现，一般需要18-24个月，并且可能只在40-45岁以下的成人中出现。因此作者指出，可以加快或者促进老年人广泛T细胞受体库恢复的策略可能有助于大量临床应用。
在初期和动物实验中，IL-7治疗显示明显的重建T细胞免疫作用，在小鼠中还能增强对疫苗的效应和记忆反应，与抗肿瘤疫苗联合使用，IL-7治疗还能增强抗肿瘤反应。 rhIL-7的临床应用前景很广阔，但是也可能失败。1期剂量增加实验中，美国马里兰州国家癌症研究院癌症研究、实验移植和免疫中心的Claude Sportès博士及其同事选取16名患者，评价IL-7治疗对人类淋巴细胞的影响，这些患者20-71岁，没有血液学和淋巴细胞难治性癌症。隔天皮下注射，剂量逐渐增加，持续14天。 结果发现一个很短暂的降低后，循环淋巴细胞和CD4+、CD8+T细胞数量都呈剂量依赖的方式增加。最高剂量水平的时候，CD4+细胞增加300%，CD8+T细胞增加400%。总之，治疗可以诱导广泛的T细胞循环，能够在保留T细胞功能的同时扩大人类患者的T细胞库。
使用rhIL-7治疗也比rhIL-2有优势，扩增的T细胞保留明显的功能活性，CD4+T细胞扩增不伴有不成比例的调节性T细胞增加，而调节性T细胞比例增加是IL-2治疗的一个现象。先前资料表明人类体内使用IL-2对于CD8+T细胞水利影响很小，而rhIL-7对于CD8+T细胞扩增与CD4+T细胞类似。（生物谷Bioon.com）
生物谷推荐原始出处：
Journal of Experimental Medicine，Vol. 205, No. 7, 1701-1714，Claude Sportès，Crystal L. Mackall
Administration of rhIL-7 in humans increases in vivo TCR repertoire diversity by preferential expansion of naive T cell subsets
Claude Sportès1, Frances T. Hakim1, Sarfraz A. Memon1, Hua Zhang2, Kevin S. Chua2, Margaret R. Brown4, Thomas A. Fleisher4, Michael C. Krumlauf1, Rebecca R. Babb1, Catherine K. Chow3, Terry J. Fry2, Julie Engels5, Renaud Buffet5, Michel Morre5, Robert J. Amato6, David J. Venzon7, Robert Korngold8, Andrew Pecora8, Ronald E. Gress1, and Crystal L. Mackall2
1 Experimental Transplantation and Immunology Branch; 2 Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute; 3 Departments of Radiology; 4 Department of Laboratory Medicine, Clinical Center, National Institutes of Health, Bethesda, MD 20892
5 Cytheris Inc., Rockville, MD 20850
6 Methodist Hospital, Texas Medical Center, Houston, TX 77021
7 Biostatistics and Data Management Section, National Cancer Institute, 8 The Cancer Center at Hackensack University Medical Center, Hackensack, NJ 07601
CORRESPONDENCE Claude Sportès: csportes@mail.nih.gov
Interleukin-7 (IL-7) is a homeostatic cytokine for resting T cells with increasing serum and tissue levels during T cell depletion. In preclinical studies, IL-7 therapy exerts marked stimulating effects on T cell immune reconstitution in mice and primates. First-in-human clinical studies of recombinant human IL-7 (rhIL-7) provided the opportunity to investigate the effects of IL-7 therapy on lymphocytes in vivo. rhIL-7 induced in vivo T cell cycling, bcl-2 up-regulation, and a sustained increase in peripheral blood CD4+ and CD8+ T cells. This T cell expansion caused a significant broadening of circulating T cell receptor (TCR) repertoire diversity independent of the subjects' age as naive T cells, including recent thymic emigrants (RTEs), expanded preferentially, whereas the proportions of regulatory T (T reg) cells and senescent CD8+ effectors diminished. The resulting composition of the circulating T cell pool more closely resembled that seen earlier in life. This profile, distinctive among cytokines under clinical development, suggests that rhIL-7 therapy could enhance and broaden immune responses, particularly in individuals with limited naive T cells and diminished TCR repertoire diversity, as occurs after physiological (age), pathological (human immunodeficiency virus), or iatrogenic (chemotherapy) lymphocyte depletion.
