Wang Xiaolei, Rasmussen Terri, Pahar Bapi, Poonia Bhawna, Alvarez Xavier, Lackner Andrew A, Veazey Ronald S
Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433, USA.
Blood. 2007 Feb 1;109(3):1174-81. doi: 10.1182/blood-2006-04-015172. Epub 2006 Oct 17.
Rapid, profound, and selective depletion of memory CD4+ T cells has now been confirmed to occur in simian immunodeficiency virus (SIV)-infected adult macaques and human immunodeficiency virus (HIV)-infected humans. Within days of infection, marked depletion of memory CD4+ T cells occurs primarily in mucosal tissues, the major reservoir for memory CD4+ T cells in adults. However, HIV infection in neonates often results in higher viral loads and rapid disease progression, despite the paucity of memory CD4+ T cells in the peripheral blood. Here, we examined the immunophenotype of CD4+ T cells in normal and SIV-infected neonatal macaques to determine the distribution of naive and memory T-cell subsets in tissues. We demonstrate that, similar to adults, neonates have abundant memory CD4+ T cells in the intestinal tract and spleen and that these are selectively infected and depleted in primary SIV infection. Within 12 days of SIV infection, activated (CD69+), central memory (CD95+CD28+) CD4+ T cells are marked and persistently depleted in the intestine and other tissues of neonates compared with controls. The results in dicate that "activated" central memory CD4+ T cells are the major target for early SIV infection and CD4+ T cell depletion in neonatal macaques.
现已证实，在感染猿猴免疫缺陷病毒（SIV）的成年猕猴和感染人类免疫缺陷病毒（HIV）的人类中，记忆性CD4+ T细胞会迅速、显著且选择性地耗竭。在感染后的数天内，记忆性CD4+ T细胞的显著耗竭主要发生在黏膜组织中，而黏膜组织是成年人记忆性CD4+ T细胞的主要储存库。然而，尽管新生儿外周血中记忆性CD4+ T细胞数量稀少，但HIV感染往往会导致更高的病毒载量和疾病快速进展。在此，我们检测了正常和感染SIV的新生猕猴中CD4+ T细胞的免疫表型，以确定幼稚和记忆性T细胞亚群在组织中的分布。我们证明，与成年人相似, 新生儿在肠道和脾脏中有丰富的记忆性CD4+ T细胞，并且在初次感染SIV时这些细胞会被选择性感染和耗竭。与对照组相比，在感染SIV的12天内，新生猕猴肠道和其他组织中活化的（CD69+）、中央记忆性（CD95+CD28+）CD4+ T细胞显著且持续耗竭。结果表明，“活化的”中央记忆性CD4+ T细胞是新生猕猴早期SIV感染和CD4+ T细胞耗竭的主要靶标。
