Sousa, Ana E.Chaves, Ana F.Doroana, ManuelaAntunes, FranciscoVictorino, Rui M. M.2014-06-042014-06-042000Clinical Immunology, Vol. 97, No. 2, November, pp. 162–170, 20001521-6616http://dx.doi.org/10.1006/clim.2000.4930http://hdl.handle.net/10451/11129http://www.sciencedirect.com/science/article/pii/S1521661600949301Copyright © 2000, ElsevierCytokine 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.engHIVCytokinesAntiretroviral therapyImmunological reconstitutionIntracellular cytokine detectionBulk cytokine production versus frequency of cytokine-producing cells in HIV1 infection before and during HAARTjournal article