Kinetics of CD4+ T cell repopulation of lymphoid tissues after treatment of HIV-1 infection

Zhi Qiang Zhang, Daan W. Notermans, Gerald Sedgewick, Winston Cavert, Stephen Wietgrefe, Mary Zupancic, Kristin Gebhard, Keith Henry, Lawrence Boies, Zongming Chen, Marc Jenkins, Roger Mills, Hugh Mcdade, Carolyn Goodwin, Caspar M. Schuwirth, Sven A. Danner, Ashley T. Haase*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Potent combinations of antiretroviral drugs diminish the turnover of CD4+ T lymphocytes productively infected with HIV-1 and reduce the large pool of virions deposited in lymphoid tissue (LT). To determine to what extent suppression of vital replication and reduction in viral antigens in LT might lead correspondingly to repopulation of the immune system, we characterized CD4+ T lymphocyte populations in LT in which we previously had quantitated viral load and turnover of infected cells before and after treatment. We directly measured by quantitative image analysis changes in total CD4+ T cell counts, the CD45RA+ subset, and fractions of proliferating or apoptotic CD4+ T cells. Compared with normal controls, we documented decreased numbers of CD4+ T cells and increased proliferation and apoptosis. After treatment, proliferation returned to normal levels, and total CD4+ T and CD45RA+ cells increased. We discuss the effects of HIV-1 on this subset based on the concept that renewal mechanisms in the adult are operating at full capacity before infection and cannot meet the additional demand imposed by the loss of productively infected cells. The slow increases in the CD45RA+ CD4+ T cells are consistent with the optimistic conclusions that (i) renewal mechanisms have not been damaged irreparably even at relatively advanced stages of infection and (ii) CD4+ T cell populations can be partially restored by control of active replication without eradication of HIV-1.

Original languageEnglish
Pages (from-to)1154-1159
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number3
DOIs
Publication statusPublished - 3 Feb 1998

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