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Blood, Vol. 96 No. 1 (July 1), 2000:
pp. 242-249
T-cell progenitor function during progressive human
immunodeficiency virus-1 infection and after antiretroviral therapy
Dawn R. Clark,
Sjoerd Repping,
Nadine G. Pakker,
Jan M. Prins,
Daan W. Notermans,
Ferdinand W. N. M. Wit,
Peter Reiss,
Sven A. Danner,
Roel A. Coutinho,
Joep M. A. Lange, and
Frank Miedema
From the Department of Clinical Viro-Immunology, Laboratory for
Experimental and Clinical Immunology, CLB, Sanquin Blood Supply
Foundation, the National AIDS Therapy Evaluation Center, the Division
of Infectious Diseases, Tropical Medicine and AIDS, and the Department
of Internal Medicine, Academic Medical Centre, and the Department of
Public Health, Municipal Health Service, Amsterdam, The Netherlands.
Impairment of T-cell renewal has been proposed as contributing to
CD4+ T-cell depletion in persons infected with human
immunodeficiency virus-1. We analyzed the T-cell development capacity
of progenitors using fetal thymus organ culture. Those who progressed
to AIDS had a dramatic loss in T-cell development capacity shortly
after seroconversion. In contrast, long-term nonprogressors retained progenitor capacity 8 years after seroconversion. Approximately 70% of
patients experienced an improvement in T-cell development capacity
after receiving 6 months of potent antiretroviral therapy. Improvement
in T-cell development in fetal thymus organ culture correlated with an
increase in the number of naive CD4+ T cells in
peripheral blood. Numbers of progenitors in blood and bone marrow after
seroconversion or during therapy did not correlate with the change
observed in T-cell development capacity. These data provide evidence
that HIV-1 infection can interfere with T-cell renewal at the level of
the progenitor cell. Interference with T-cell renewal may contribute to
CD4+ T-cell depletion.
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