Memory CD4+ T-lymphocyte loss and dysfunction during primary simian immunodeficiency virus infection.
It has long been appreciated that CD4+ T lymphocytes are dysfunctional in human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV)-infected individuals, and it has recently been shown that HIV/SIV infections are associated with a dramatic early destruction of memory CD4+ T lymphocytes. However, the relative contributions of CD4+ T-lymphocyte dysfunction and loss to immune dysregulation during primary HIV/SIV infection have not been fully elucidated. In the current study, we evaluated CD4+ T lymphocytes and their functional repertoire during primary SIVmac251 infection in rhesus monkeys. We show that the extent of loss of memory CD4+ T lymphocytes and staphylococcal enterotoxin B-stimulated cytokine production by total CD4+ T lymphocytes during primary SIVmac251 infection is tightly linked in a cohort of six rhesus monkeys to set point plasma viral RNA levels, with greater loss and dysfunction being associated with higher steady-state viral replication. Moreover, in exploring the mechanism underlying this phenomenon, we demonstrate that the loss of functional CD4+ T lymphocytes during primary SIVmac251 infection is associated with both a selective depletion of memory CD4+ T cells and a loss of the functional capacity of the memory CD4+ T lymphocytes that escape viral destruction.
Sun
Yue
Y
Division of Viral Pathogenesis, Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
Permar
Sallie R
SR
Buzby
Adam P
AP
Letvin
Norman L
NL
D000818:Animals; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D015683:Gene Products, gag / Q000276:immunology; D006678:HIV / Q000276:immunology; D006801:Humans; D007156:Immunologic Memory / Q000502:physiology*; D008253:Macaca mulatta; D012367:RNA, Viral / Q000097:blood; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D016176:T-Lymphocyte Subsets / Q000378:metabolism
D015683:Gene Products, gag; D012367:RNA, Viral