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Blood, Vol. 95 No. 1 (January 1), 2000:
pp. 249-255
T-cell division in human immunodeficiency virus (HIV)-1
infection is mainly due to immune activation: a longitudinal
analysis in patients before and during highly active antiretroviral
therapy (HAART)
Mette D. Hazenberg,
James W. T. Cohen Stuart,
Sigrid A. Otto,
Jan C. C. Borleffs,
Charles A. B. Boucher,
Rob J. de Boer,
Frank Miedema, and
Dörte Hamann
From the Department of Clinical Viro-Immunology, CLB, and the
Laboratory for Experimental and Clinical Immunology and Department of
Human Retrovirology, Academic Medical Center, University of
Amsterdam, Amsterdam; the Department of Internal Medicine, University
Hospital Utrecht; the Department of Virology, Eijkman-Winkler
Institute, University Hospital Utrecht; and the Department of
Theoretical Biology, Utrecht University, Utrecht, The Netherlands.
In human immunodeficiency virus (HIV)-1 infection, highly
increased T-cell turnover was proposed to cause exhaustion of
lymphocyte production and consequently development of AIDS. Here, we
investigated cell proliferation, as measured by expression of the Ki-67
nuclear antigen, in peripheral blood CD4+ and
CD8+ lymphocyte subpopulations before and during highly
active antiretroviral therapy (HAART). In untreated HIV-1
infection, both the percentage and number of Ki-67+
CD4+ and CD8+ lymphocytes were
significantly increased, compared with values obtained from
healthy individuals. A more than 10-fold increase in the percentage of
dividing naive CD4+ T cells in the blood was found
when the number of these cells were below 100 per µL.. HAART
induced an immediate decline in Ki-67 antigen expression, despite often
very low CD4+ T-cell numbers, arguing against increased
proliferation being a homeostatic response. After approximately 24 weeks of HAART treatment, a transient increase in the number of
proliferating cells was seen, but only in the CD4+
CD27+ memory pool. In the CD8+ T-cell
compartment, the number of dividing cells was elevated 20- to
25-fold. This increase was most notable in the CD27+ CD
45RO+ and CD27
CD45RO+ memory CD8+ T-cell pool,
corresponding with the degree of expansion of these subsets. Reduction
of plasma HIV-RNA load by HAART was accompanied by a decrease in
numbers and percentages of dividing cells in all CD8+
T-cell subsets. Taken together, our results indicate that peripheral T-cell proliferation is a consequence of generalized immune activation. (Blood. 2000;95:249-255)
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