Impaired proliferative capacity and abnormal cytokine profile of naive and memory CD4 T cells from HIV-seropositive patients

Abstract

SUMMARYPurified naive and memory CD4 T cells from healthy donors, HIV+ asymptomatic carriers and AtDS patients were examined for their proliferative activity and their pattern of cytokine secretion (IL-4, IL-6, interferon-gamma (IFN-y) and tumour necrosis factor-alpha (TNF-a)) upon stimulation with phytohaemagglutinin (PHA), phorbol myristate acetate (PMA) and cross-linked anti-CD3 MoAb, in the presence of recombinant IL-2 (rIL-2). We found a decrease in the proliferative capacity ofnaive CD4 T cells following stimulation with PHA and PMA, and a sharp decline in this response upon cross-linked anti-CD3 stimulation in both subsets, although it predominated in the naive subpopulation. In AIDS patients, less pronounced impairment of thymidine uptake by the naive subset was found upon PHA and cross-linked anti-CD3 MoAb stimulation. In addition, an altered secretion pattern ofthe different cytokines was observed, consisting of abnormal secretion of IL-6 by both naive and memory cells, an abnormal pattern of IFN-y secretion and frequent loss of detectable lL-4 production by HIV patients. These abnormalities were even more pronounced in AIDS patients than in the asymptomatic carriers. Overall, our results extend previous reports indicating functional impairment of memory CD4 subsets in HIV+ subjects by showing that this impairment involves naive CD4 T cells.

The comparison of Th1, Th2, Th9, Th17 and Th22 cytokine profiles in acute and chronic HIV-1 infection

“…IL-6 is a cytokine with various biological functions including B-cell stimulation, monocyte differentiation and induction of IL-4 producing cells. In vitro data in mitogen-stimulated CD4+ T-cells from HIV-infected individuals showed increased synthesis of IL-6 [32] and [33]. The results of our study also demonstrated increased levels of this cytokine in chronic HIV-1 infection which is consistent with literature data.…”

Natural killer (NK) cell activity during HIV infection: a decrease in NK activity is observed at the clonal level and is not restored afterin vitrolong-term culture of NK cells

“…Robinson et al [29] found a decrease in NK activity following in vitro infection of these cells by HIV, whereas Chehimi et al [30] [31] are in agreement with the hypothesis of a 'general anergic process' during HIV infection which cannot be accounted for by the cytopathic effect of HIV. Proteins of the HIV-1 virus have been shown to have important immunomodulating properties, which may still be observed after long-term culture.…”

Increased soluble CD14 serum levels and altered CD14 expression of peripheral blood monocytes in HIV-infected patients

“…Expression of membrane-bound CDi4 and release of soluble CD14 by monocytes is down-regulated by T cellderived IL-4 and interferon-gamma (IFN-7) [35,36]. T lymphocytes from HIV-infected patients express [37,38] and secrete [39] IFN--, at an increased rate, but are unable to produce iL-4 [39]. In this regard it is of interest thai both cyiokines modulating CD14 derive from different subsets of T helper cells, IFN-7 from Thl and IL-4 from Th2 cells.…”

“…T lymphocytes from HIV-infected patients express [37,38] and secrete [39] IFN--, at an increased rate, but are unable to produce iL-4 [39]. In this regard it is of interest thai both cyiokines modulating CD14 derive from different subsets of T helper cells, IFN-7 from Thl and IL-4 from Th2 cells.…”