Mucosal immunization in macaques upregulates the innate APOBEC 3G anti-viral factor in CD4(+) memory T cells.
Mucosal immunization in macaques upregulates the innate APOBEC 3G anti-viral factor in CD4(+) memory T cells.
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猕猴的粘膜免疫上调 CD4(+) 记忆 T 细胞中先天的 APOBEC 3G 抗病毒因子。
DOI：
10.1016/j.vaccine.2008.11.084
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发表时间：
2009
期刊：
影响因子：
5.5
通讯作者：
Lehner,Thomas
中科院分区：
文献类型：
--
作者：
Wang,Yufei;Bergmeier,LesleyA;Stebbings,Richard;Seidl,Thomas;Whittall,Trevor;Singh,Mahavir;Berry,Neil;Almond,Neil;Lehner,Thomas
APOBEC3G 是一种先天性细胞内抗病毒因子，可将逆转录病毒胞苷脱氨基为尿苷。使用与 70kDa 热休克蛋白相连的 SIV 抗原和 CCR5 肽进行粘膜免疫后，在恒河猴中进行了 APOBEC3G (A3G) 的体内研究。每次免疫后，PBMC 中 A3G mRNA 逐渐增加（p<0.0002 至 p≤0.02），并维持至少 17 周。记忆T细胞分析显示，与未免疫的猕猴相比，免疫的猕猴的循环（p=0.0001）、脾（p=0.0001）、髂淋巴结（p=0.002）和直肠（p=0.01）细胞中CD4+CCR5+记忆T细胞的A3G mRNA和蛋白显着增加。用 SIVmac 251 进行的粘膜攻击显示，免疫的未感染猕猴中 CD4+CCR5+ 循环细胞 (p<0.01) 和引流髂淋巴结细胞 (p<0.05) 中的 A3G mRNA 显着增加，这与 A3G 发挥的保护作用一致。结果表明，非人灵长类动物的粘膜免疫可以诱导 CCR5+CD4+记忆和 CD4+CD95+CCR7-效应记忆 T 细胞对先天抗病毒因子的记忆反应特征。
APOBEC3G is an innate intracellular anti-viral factor which deaminates retroviral cytidine to uridine. In vivo studies of APOBEC3G (A3G) were carried out in rhesus macaques, following mucosal immunization with SIV antigens and CCR5 peptides, linked to the 70kDa heat shock protein. A progressive increase in A3G mRNA was elicited in PBMC after each immunization (p<0.0002 to p≤0.02), which was maintained for at least 17 weeks. Analysis of memory T cells showed a significant increase in A3G mRNA and protein in CD4+CCR5+memory T cells in circulating (p=0.0001), splenic (p=0.0001), iliac lymph nodes (p=0.002) and rectal (p=0.01) cells of the immunized compared with unimmunized macaques. Mucosal challenge with SIVmac 251 showed a significant increase in A3G mRNA in the CD4+CCR5+circulating cells (p<0.01) and the draining iliac lymph node cells (p<0.05) in the immunized uninfected macaques, consistent with a protective effect exerted by A3G. The results suggest that mucosal immunization in a non-human primate can induce features of a memory response to an innate anti-viral factor in CCR5+CD4+memory and CD4+CD95+CCR7−effector memory T cells.