Comparison of the frequency of interleukin (IL)-2-, interferon-gamma-, and IL-4-producing T cells in 2 diseases, human immunodeficiency virus types 1 and 2, with distinct clinical outcomes.

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)-gamma-, 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-gamma(+)). However, the proportion of CD8 T cells able to simultaneously produce IL-2 and IFN-gamma 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.

Bulk cytokine production versus frequency of cytokine-producing cells in HIV1 infection before and during HAART.

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-gamma(+) lymphocytes and bulk IFN-gamma 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-gamma, which is consistent with a large variation in the amount of IFN-gamma released per individual cell. Moreover, HAART was associated with a reduction to normal levels in the bulk IFN-gamma secretion concomitant with a persistency of the overexpanded IFN-gamma(+) 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.

Early reduction of the over-expression of CD40L, OX40 and Fas on T cells in HIV-1 infection during triple anti-retroviral therapy: possible implications for lymphocyte traffic and functional recovery.

Fas, CD40L and OX40 are members of the tumour necrosis factor (TNF) receptor superfamily with critical roles in T cell activation and death, B cell function, dendritic cell maturation and leucocyte traffic regulation. The aim of this study was to evaluate the effects of anti-retroviral therapy (HAART) on CD40L, OX40 and Fas expression on freshly isolated peripheral blood T cells by three-colour flow cytometry and compare them with lymphoproliferative responses, peripheral blood cell counts and viral load. Fourteen asymptomatic HIV-1+ patients treated with Lamivudine, Stavudine and Nelfinavir were prospectively investigated sequentially for 48 weeks. At baseline, patients exhibited significantly enhanced proportions and counts of CD40L+ and OX40+ cells within the CD4 subset which were corrected by weeks 8-16 of HAART. Interestingly, in the five patients showing viral load rebound during therapy in spite of increasing CD4 counts, the reduction of the levels of these costimulatory molecules was similarly maintained. Therapy induced a decrease in the over-expression of Fas, particularly in the CD4 subset where normal levels were reached at week 8. This reduction occurred in parallel with the major recovery of lymphoproliferative responses. Higher basal levels and lower reduction of Fas were associated with suboptimal suppression of viraemia. In conclusion, this previously undescribed increased expression of CD40L and OX40 may play a role in the HIV-associated pan-immune activation and represent a possible target for immunointervention, as suggested for several immunologically mediated diseases. Moreover, HAART induced an early correction of the over-expression of Fas, CD40L and OX40 in CD4 T cells which could be involved in the recovery of the cell traffic disturbances and in the T cell renewal capacity.

Kinetics of the changes of lymphocyte subsets defined by cytokine production at single cell level during highly active antiretroviral therapy for HIV-1 infection.

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-gamma + 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.

Efeitos secundarios das resseccoes intestinais extensas. / Secondary effects of extensive intestinal resections

A retirada de longos segmentos intestinais se acompanha de alteracoes morfologicas e funcionais, procurando fazer com que o organismo se adapte a nova situacao estabelecida. Inumeras sao as consequencias das resseccoes intestinais extensas, algumas indesejaveis, interferindo na evolucao e no prognostico de grande enterectomizado.Neste artigo sao analisados os efeitos das resseccoes intestinais extensas no segmento intestinal remanescente, no intestino grosso, na secrecao gastrica e no "pool" de sal biliar

Nutricao parenteral domiciliar. / Home parenteral nutrition

A nutricao parenteral tem ganho campo de aplicacao cada vez maior e seu emprego a domicilio, de forma temporaria ou definitiva, tem permitido manter adequadamente o estado nutricional de doentes impossibilitados da utilizacao do trato digestivo.Neste artigo, sao discutidas as indicacoes os aspectos tecnicos e as complicacoes da nutricao parenteral domiciliar e apresentados dois doentes que se beneficiaram desse metodo