Browsing by Author "Chaves, Ana F."
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- Bulk cytokine production versus frequency of cytokine-producing cells in HIV1 infection before and during HAARTPublication . Sousa, Ana E.; Chaves, Ana F.; Doroana, Manuela; Antunes, Francisco; Victorino, Rui M. M.Cytokine imbalances play a major role in HIV immunopathogenesis. This study analyzes simultaneously the frequency of cytokine-producing cells at the single cell level by flow cytometry and the disturbances in cytokine secretion assessed by ELISA in a cohort of asymptomatic HIV1 patients in different stages of CD4 depletion and during antiretroviral therapy (HAART). Early in the disease, there is an increased frequency of IFN-γ lymphocytes and bulk IFN-γ+ production, in parallel with a reduced proportion of IL4+ cells and IL4 secreted. The two IL4 measurements are significantly correlated. No such correlation was found for IFN-γ, which is consistent with a large variation in the amount of IFN-γ released per individual cell. Moreover, HAART was associated with a reduction to normal levels in the bulk IFN-γ secretion concomitant with a persistency of the overexpanded IFN-γ+ cell subset in the peripheral blood. This study emphasizes the importance of using a conjoint approach to assess the cytokine network in trials of antiretroviral and/or immune-based therapies to avoid missing significant effects which are possibly relevant in the clinical setting.
- Comparison of the frequency of interleukin (IL)-2-, interferon-γ-, and IL-4-producing T cells in 2 diseases, human immunodeficiency virus types 1 and 2, with distinct clinical outcomesPublication . Sousa, Ana E.; Chaves, Ana F.; Loureiro, Ana; Victorino, Rui M. M.Human immunodeficiency virus (HIV) type 2 infection is associated with a better clinical outcome, slower rates of CD4 T cell decline, and lower viremia than is HIV-1. This study compares HIV-1 and HIV-2 in regard to the percentages of interleukin (IL)–2–, interferon (IFN)–γ–, and IL-4–producing cells at the single-cell level, as determined by flow cytometry. At a given degree of CD4 T cell depletion, the frequency of T cells able to produce IL-2 is better preserved in HIV-2 than in HIV-1 infection, particularly within the CD4 T cell subset. As described for HIV-1 immunodeficiency, HIV-2–positive patients exhibit a marked expansion of terminally differentiated effector CD8 T cells (CD28−CD27−IFN-γ+). However, the proportion of CD8 T cells able to simultaneously produce IL-2 and IFN-γ is higher in HIV-2 disease. Considering the central role of IL-2 as a lymphocyte proliferative and survival factor, these findings provide a possible immunologic basis for the distinct course of HIV-2 immunodeficiency