Impact of simian immunodeficiency virus (SIV) infection on lymphocyte numbers and T-cell turnover in different organs of rhesus monkeys.
HIV infection leads to reduced numbers and increased turnover of CD4(+) T cells in blood. However, blood represents only 2% of the total lymphocyte pool, and information about other organs is lacking, leading to controversy about the effects of HIV infection on T-cell homeostasis. Therefore, we have determined phenotype and turnover of lymphocyte subsets in various tissues of macaques. Infection with simian immunodeficiency virus (SIV) resulted in increased proliferation rates of T cells in all organs. Despite reduced CD4 counts in blood, absolute numbers of CD4(+) T cells were increased in spleen and lymph nodes and remained stable in nonlymphoid organs such as liver, lung, bone marrow, and brain during the asymptomatic phase, indicative for an altered tissue distribution. In animals killed with first signs of AIDS, total body CD4 counts and proliferation rates had returned to control levels, whereas thymocytes were almost completely absent. Our data show that a drastically increased turnover in the early stages of HIV infection, driven by a generalized immune activation rather than a homeostatic response to CD4(+) T-cell destruction, is followed by exhaustion of the regenerative capacity of the immune system.
Sopper
Sieghart
S
Institut für Virologie und Immunbiologie, Julius-Maximilians-Universität, Würzburg, Germany. sopper@vim.uni-wuerzburg.de
Nierwetberg
Dagmar
D
Halbach
Astrid
A
Sauer
Ursula
U
Scheller
Carsten
C
Stahl-Hennig
Christiane
C
Mätz-Rensing
Kerstin
K
Schäfer
Frank
F
Schneider
Thomas
T
ter Meulen
Volker
V
Müller
Justus G
JG
D000818:Animals; D001853:Bone Marrow / Q000276:immunology; D001921:Brain / Q000276:immunology; D018791:CD4 Lymphocyte Count; D016516:CD4-CD8 Ratio; D008099:Liver / Q000276:immunology; D008168:Lung / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology; D008213:Lymphocyte Activation; D018655:Lymphocyte Count; D008253:Macaca mulatta; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology