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Cellular Immunology Unit, Centre for Biology and Molecular Pathology, Faculty of Medicine of Lisbon, Lisbon, Portugal; and Departments of
Infectious Diseases and
Medicine 2, Faculty of Medicine of Lisbon/University Hospital of Santa Maria, Lisbon, Portugal
The effects of highly active antiretroviral therapy on
cytokine imbalances associated with HIV-1 infection have not been
characterized. Using single cell analysis by flow cytometry, we show
that a significant recovery in the frequency of IL-2-producing cells
was only observed in patients with a sustained control of viral
replication and that the overexpanded CD8 T cell population of
CD28- IFN-
+ cells was not significantly
reduced after 1 yr of effective therapy. Moreover, a detrimental role
of IL-4 is suggested by the association between an enhanced proportion
of IL-4-producing cells within the CD4 and particularly the CD8 subset
and viral load rebound. Finally, the kinetics of changes of cell
subsets assessed for simultaneous production of different cytokines
supports the view that cell reconstitution during highly active
antiretroviral therapy is initially due to redistribution of terminally
differentiated cells, followed by peripheral expansion of less
differentiated ones and a late progressive increase of the proportion
of functionally defined naive/memory precursor lymphocytes. These data
bring new support for the role of cytokine imbalances in AIDS
pathogenesis and may be relevant for the definition of
immunointervention targets.
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