T cell regeneration in HIV-infected subjects under highly active antiretroviral therapy (review).
The initial idea that high amounts of cytopathic virus produced everyday can drive high CD4+ T cell production seemed logical and explained the progressive CD4+ T cell depletion observed in HIV-infected subjects. It was hypothesized that the CD4+ T lymphocyte production was increased up to 70-fold in HIV-infected subjects. Determination of the CD4+ T cell production was based on the kinetics of CD4+ T cell recovery following initiation of highly active antiretroviral therapy (HAART). However, this analysis is limited by: i) the assumption that blood CD4+ T cells are representative of the lymph node T cells; and ii) the lack of estimates of CD4+ T lymphocyte turnover in healthy HIV-negative subjects. Several immunologists have expressed caution regarding the assumptions used in modeling CD4+ T cell dynamics. Recent findings clearly show that blood is not representative of lymphoid tissues and invalidate the conclusion of high CD4 turnover drawn from blood studies on HIV-infected subjects. Indeed, when blood and lymph node compartments are considered together, we find that HIV-infected subjects naive to antiretroviral have similar or lower CD4+ T cell production, as compared to healthy subjects. This observation suggests an impaired T cell renewal capacity in HIV-1 infected patients.
Fleury
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S
Laboratory of AIDS Immunopathogenesis, Department of Medicine, Division of Infectious Diseases, CH-1011 Lausanne, Switzerland.
Pantaleo
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G
D019380:Anti-HIV Agents / Q000627:therapeutic use*; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects* / Q000276:immunology* / Q000473:pathology; D002455:Cell Division; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D006706:Homeostasis; D006801:Humans; D007156:Immunologic Memory; D008213:Lymphocyte Activation; D008954:Models, Biological
D019380:Anti-HIV Agents