Increased rates of CD4(+) and CD8(+) T lymphocyte turnover in simian immunodeficiency virus-infected macaques.
Defining the rate at which T cells turn over has important implications for our understanding of T lymphocyte homeostasis and AIDS pathogenesis, yet little information on T cell turnover is available. We used the nucleoside analogue bromodeoxyuridine (BrdUrd) in combination with five-color flow cytometric analysis to evaluate T lymphocyte turnover rates in normal and simian immunodeficiency virus (SIV)-infected rhesus macaques. T cells in normal animals turned over at relatively rapid rates, with memory cells turning over more quickly than naive cells. In SIV-infected animals, the labeling and elimination rates of both CD4(+) and CD8(+) BrdUrd-labeled cells were increased by 2- to 3-fold as compared with normal controls. In normal and SIV-infected animals, the rates of CD4(+) T cell BrdUrd-labeling and decay were closely correlated with those of CD8(+) T cells. The elimination rate of BrdUrd-labeled cells was accelerated in both naive and memory T lymphocytes in SIV-infected animals. Our results provide direct evidence for increased rates of both CD4(+) and CD8(+) T cell turnover in AIDS virus infection and have important implications for our understanding of T cell homeostasis and the mechanisms responsible for CD4(+) T cell depletion in AIDS.
Rosenzweig
M
M
Division of Immunology, New England Regional Primate Research Center, Harvard Medical School, P.O. Box 9102, One Pine Hill Drive, Southborough, MA 01772, USA.
DeMaria
M A
MA
Harper
D M
DM
Friedrich
S
S
Jain
R K
RK
Johnson
R P
RP
D000818:Animals; D016516:CD4-CD8 Ratio; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology; D002455:Cell Division; D003602:Cytotoxicity, Immunologic; D005434:Flow Cytometry; D018655:Lymphocyte Count; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*