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)

Author:

Hazenberg Mette D.1,Stuart James W. T. Cohen1,Otto Sigrid A.1,Borleffs Jan C. C.1,Boucher Charles A. B.1,de Boer Rob J.1,Miedema Frank1,Hamann Dörte1

Affiliation:

1. 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.

Abstract

Abstract 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)

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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