Massive infection and loss of CD4+ T cells occurs in the intestinal tract of neonatal rhesus macaques in acute SIV infection

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 indicate that activated central memory CD4(+) T cells are the major target for early SIV infection and CD4(+) T cell depletion in neonatal macaques.