Transient and persistent effects of IL-15 on lymphocyte homeostasis in nonhuman primates
Transient and persistent effects of IL-15 on lymphocyte homeostasis in nonhuman primates
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DOI：
10.1182/blood-2010-03-275438
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发表时间：
2010-10-28
期刊：
影响因子：
20.3
通讯作者：
Roederer, Mario
中科院分区：
文献类型：
--
作者：
Lugli, Enrico;Goldman, Carolyn K.;Roederer, Mario
白介素15(IL-15)是一种细胞因子，在癌症或免疫缺陷患者中具有潜在的治疗应用价值，可促进自然杀伤(NK)和T细胞的激活和增殖，或用于疫苗接种以产生长寿记忆T细胞。在这里，我们报告了每天给恒河猴静脉注射10-50微克/公斤IL-15，连续12天，对T细胞稳态有短期和长期的影响。外周血淋巴细胞减少先于循环中NK细胞和记忆性CD8T细胞的急剧扩张，特别是中央记忆性CD8T细胞扩大4倍，效应记忆CD8T细胞扩大6倍。这种扩张是它们在多个组织中激活的结果。在第13天，由于CD8的优先扩增，全身观察到伴随的CD4/CD8T细胞比率倒置。在IL-15停止后不久，血液中扩大的T细胞和NK细胞数量下降，表明迁移到淋巴外部位。到第48天，全身似乎恢复了动态平衡，但淋巴结中的CD4/CD8比率保持了倒置。因此，IL-15在免疫功能正常的猕猴体内产生短期记忆的CD8 T细胞和NK细胞的急剧扩张，并对CD4(+)和CD8(+)T细胞的平衡产生长期影响。(血。2010；116(17)：3238-3248)
Interleukin-15 (IL-15) is a cytokine with potential therapeutic application in individuals with cancer or immunodeficiency to promote natural killer (NK)- and T-cell activation and proliferation or in vaccination protocols to generate long-lived memory T cells. Here we report that 10-50 mu g/kg IL-15 administered intravenously daily for 12 days to rhesus macaques has both short-and long-lasting effects on T-cell homeostasis. Peripheral blood lymphopenia preceded a dramatic expansion of NK cells and memory CD8 T cells in the circulation, particularly a 4-fold expansion of central memory CD8 T cells and a 6-fold expansion of effector memory CD8 T cells. This expansion is a consequence of their activation in multiple tissues. A concomitant inverted CD4/CD8 T-cell ratio was observed throughout the body at day 13, a result of preferential CD8 expansion. Expanded T-and NK-cell populations declined in the blood soon after IL-15 was stopped, suggesting migration to extra-lymphoid sites. By day 48, homeostasis appears restored throughout the body, with the exception of the maintenance of an inverted CD4/CD8 ratio in lymph nodes. Thus, IL-15 generates a dramatic expansion of short-lived memory CD8 T cells and NK cells in immunocompetent macaques and has long-term effects on the balance of CD4(+) and CD8(+) T cells. (Blood. 2010; 116(17):3238-3248)