Memory CD4 super(+) T-Lymphocyte Loss and Dysfunction during Primary Simian Immunodeficiency Virus Infection

• Published in: Journal of virology Vol. 81; no. 15; pp. 8009 - 8015
• Main Authors: Sun, Yue, Permar, Sallie R, Buzby, Adam P, Letvin, Norman L
• Format: Journal Article
• Language: English
• Published: 01-08-2007
• Subjects: Human immunodeficiency virus; Macaca mulatta; Simian immunodeficiency virus
• ISSN: 0022-538X; 1098-5514

It has long been appreciated that CD4 super(+) 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 super(+) T lymphocytes. However, the relative contributions of CD4 super(+) 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 super(+) T lymphocytes and their functional repertoire during primary SIVmac251 infection in rhesus monkeys. We show that the extent of loss of memory CD4 super(+) T lymphocytes and staphylococcal enterotoxin B-stimulated cytokine production by total CD4 super(+) 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 super(+) T lymphocytes during primary SIVmac251 infection is associated with both a selective depletion of memory CD4 super(+) T cells and a loss of the functional capacity of the memory CD4 super(+) T lymphocytes that escape viral destruction.