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 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.
Wang
Xiaolei
X
Tulane National Primate Research Center, Tulane University School of Medicine, Covington, LA 70433, USA.
Rasmussen
Terri
T
Pahar
Bapi
B
Poonia
Bhawna
B
Alvarez
Xavier
X
Lackner
Andrew A
AA
Veazey
Ronald S
RS
D000208:Acute Disease; D000367:Age Factors; D000818:Animals; D000831:Animals, Newborn; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000473:pathology* / Q000821:virology; D007156:Immunologic Memory; D007422:Intestines / Q000276:immunology / Q000821:virology*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D013154:Spleen / Q000821:virology