Napolitano Laura A, Schmidt Diane, Gotway Michael B, Ameli Niloufar, Filbert Erin L, Ng Myra M, Clor Julie L, Epling Lorrie, Sinclair Elizabeth, Baum Paul D, Li Kai, Killian Marisela Lua, Bacchetti Peter, McCune Joseph M
Gladstone Institute of Virology and Immunology, San Francisco, California 94158, USA.
J Clin Invest. 2008 Mar;118(3):1085-98. doi: 10.1172/JCI32830.
Growth hormone (GH) is an underappreciated but important regulator of T cell development that can reverse age-related declines in thymopoiesis in rodents. Here, we report findings of a prospective randomized study examining the effects of GH on the immune system of HIV-1-infected adults. GH treatment was associated with increased thymic mass. In addition, GH treatment enhanced thymic output, as measured by both the frequency of T cell receptor rearrangement excision circles in circulating T cells and the numbers of circulating naive and total CD4(+) T cells. These findings provide compelling evidence that GH induces de novo T cell production and may, accordingly, facilitate CD4(+) T cell recovery in HIV-1-infected adults. Further, these randomized, prospective data have shown that thymic involution can be pharmacologically reversed in humans, suggesting that immune-based therapies could be used to enhance thymopoiesis in immunodeficient individuals.
生长激素(GH)是一种未得到充分重视但对T细胞发育很重要的调节因子,它可以逆转啮齿动物中与年龄相关的胸腺生成下降。在此,我们报告一项前瞻性随机研究的结果,该研究考察了生长激素对HIV-1感染成人免疫系统的影响。生长激素治疗与胸腺质量增加有关。此外,通过循环T细胞中T细胞受体重排切除环的频率以及循环中幼稚和总CD4(+) T细胞的数量来衡量,生长激素治疗增强了胸腺输出。这些发现提供了令人信服的证据,表明生长激素可诱导新生T细胞产生,并因此可能促进HIV-1感染成人中CD4(+) T细胞的恢复。此外,这些随机、前瞻性数据表明,人类的胸腺退化可以通过药物逆转,这表明基于免疫的疗法可用于增强免疫缺陷个体的胸腺生成。