Three-color flow cytometric analysis of CD16+ natural killer (NK) cells was assessed in HIV seropositive patients and healthy heterosexual controls. A selective depletion of lymphocytes with the CD16+ NK phenotype was found among the HIV+ infected patients. When the CD16 lymphocyte subset was further evaluated by three-color flow cytometry, cells bearing both the CD8 and CD56 antigens were significantly decreased. Analysis of activation antigens revealed a large proportion of CD16+ NK cells from HIV+ patients expressed HLA-DR, but this did not correlate with CD25 (IL-2 receptor) expression. The overall loss of the CD8 and CD56 antigens among the NK population with an increase in activation status may be due to differential loss of the NK cell subsets or, alternatively, to the loss of immunoregulatory cytokines, which have been shown to be important in maintaining NK activity. Whether these changes in the NK compartment may influence the outcome of individuals with HIV disease still remains an open question but is an important issue when performing phenotypic analysis of HIV+ subjects. o 1995 Wiley-Liss, Inc.
In this study we investigate the redox profile of HIV+ patients at different stages of disease with regard to immunological parameters, i.e., the number of circulating CD4+ and CD8+ lymphocytes. For this purpose, peripheral blood mononuclear cells (PBMCs) obtained from healthy donors, HIV+ patients in the asymptomatic phase, long-term nonProgressors (LTNPs), and AIDS patients have been considered. Cells have been exposed in vitro to the prooxidizing agent menadione, which is able to induce superoxide anion formation, and the susceptibility of the cells to the induced oxidative stress was estimated. Moreover, the possibility that the susceptibility of the cells to oxidative stress might be reduced by preexposing them to the antioxidizing agent N-acetylcysteine (NAC) has also been analyzed. The results obtained can be summarized as follows: (1) treatment with the prooxidant agent is capable of inducing massive morphological alterations in PBMCs. In particular, a significant correlation was found between the decrease in number of CD4+ lymphocytes in patients at different stages of disease and the susceptibility of their PBMCs to oxidative stress; (2) preincubation with NAC was able to preserve partially the ultrastructural characteristics of PBMCs isolated from HIV+ patients. In particular, a direct relationship was found between the efficacy of NAC protection and CD4 counts; (3) evaluation of the plasma index of peroxidation and the number of circulating CD4 lymphocytes indicates the existence of a positive correlation between "systemic" oxidative imbalance and stage of the disease; and (4) cells from LTNPs display either oxidative susceptibility or oxidative markers similar to those of healthy donor cells. Our study suggests that the redox profile of patients may be considered a predictive marker of AIDS progression and that the acute infection and the asymptomatic phase of the disease may represent a useful period in which the combined use of antiretroviral and antioxidant drugs may be beneficial.
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