一項初步研究結(jié)果提示,，重組人類白介素7（rhIL-7）可以增強因為淋巴細胞去除而免疫受損的患者的免疫反應(yīng),。1期試驗結(jié)果發(fā)表在6月23日的《實驗醫(yī)學(xué)雜志》上,，研究表明在癌癥患者中使用，rhIL-7可以誘導(dǎo)CD4+和CD8+T細胞明顯的多克隆長期擴增，最終導(dǎo)致明顯的循環(huán)T細胞受體庫多樣性增加,。這些影響是通過增加外周血T細胞循環(huán)和細胞存活機制產(chǎn)生,。
細胞毒性化療引起的淋巴細胞減少或者HIV感染病理學(xué)，都可以明顯減弱免疫功能,，作為生理性免疫增強劑,，IL-7可以增強T細胞恢復(fù)。有嚴(yán)重缺乏的成人中CD4+T細胞恢復(fù)需要初始T細胞庫再現(xiàn),，一般需要18-24個月,，并且可能只在40-45歲以下的成人中出現(xiàn)。因此作者指出,，可以加快或者促進老年人廣泛T細胞受體庫恢復(fù)的策略可能有助于大量臨床應(yīng)用,。
在初期和動物實驗中，IL-7治療顯示明顯的重建T細胞免疫作用,，在小鼠中還能增強對疫苗的效應(yīng)和記憶反應(yīng),，與抗腫瘤疫苗聯(lián)合使用，IL-7治療還能增強抗腫瘤反應(yīng),。 rhIL-7的臨床應(yīng)用前景很廣闊,，但是也可能失敗。1期劑量增加實驗中,，美國馬里蘭州國家癌癥研究院癌癥研究,、實驗移植和免疫中心的Claude Sportès博士及其同事選取16名患者，評價IL-7治療對人類淋巴細胞的影響,，這些患者20-71歲,，沒有血液學(xué)和淋巴細胞難治性癌癥。隔天皮下注射,，劑量逐漸增加,，持續(xù)14天。 結(jié)果發(fā)現(xiàn)一個很短暫的降低后,，循環(huán)淋巴細胞和CD4+,、CD8+T細胞數(shù)量都呈劑量依賴的方式增加。最高劑量水平的時候,，CD4+細胞增加300%,，CD8+T細胞增加400%?？傊?，治療可以誘導(dǎo)廣泛的T細胞循環(huán)，能夠在保留T細胞功能的同時擴大人類患者的T細胞庫,。
使用rhIL-7治療也比rhIL-2有優(yōu)勢,，擴增的T細胞保留明顯的功能活性，CD4+T細胞擴增不伴有不成比例的調(diào)節(jié)性T細胞增加，而調(diào)節(jié)性T細胞比例增加是IL-2治療的一個現(xiàn)象,。先前資料表明人類體內(nèi)使用IL-2對于CD8+T細胞水利影響很小，而rhIL-7對于CD8+T細胞擴增與CD4+T細胞類似,。（生物谷Bioon.com）
生物谷推薦原始出處：
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: [email protected]
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.
