Functional Fas-ligand expression on T cells from HIV-1-infected patients is unrelated to CD4+ lymphopenia.

Important note: Information in this article was accurate in 1999. The state of the art may have changed since the publication date.

Functional Fas-ligand expression on T cells from HIV-1-infected patients is unrelated to CD4+ lymphopenia.

Int J Clin Lab Res. 1998;28(4):215-25. Unique Identifier : AIDSLINE MED/99095567
Silvestris F; Cafforio P; Camarda G; Tucci M; Frassanito MA; Dammacco F; Department of Biomedical Sciences and Human Oncology, University; of Bari, Italy.

Abstract: Recent studies have demonstrated that the expression of Fas by peripheral T cells from HIV-1+ patients is deregulated and increases the susceptibility of these cells to undergo apoptosis. Here, we show that secretion of Fas-ligand (L), the complementary agonist of Fas, is abnormally upregulated in CD4+ cells from HIV-1-infected individuals, particularly during the non-lymphopenic stages of the disease. An increase of soluble Fas-L occurred in T cell cultures from 26 patients with a number of CD4+ cells higher than 400/microliter, whereas it was almost undetectable in cultures from 21 severely lymphopenic patients (CD4+ < 200/microliter). The MTT test, cytofluorimetric analysis of cellular DNA, cytotoxicity, and proliferative assays using the Fas-transfected WC8 mouse lymphoma confirmed the cytocidal capability of T cell supernatants from non-lymphopenic patients. Double-fluorescence analysis revealed that the majority of CD4+ cells (approximately 90%) in these cultures secreted Fas-L in the presence of high intracellular gamma-interferon and low Bcl-2. In contrast, the CD8+/Fas-L+ population was comparably decreased (approximately 55%). Molecular cloning of Fas-L revealed a substantial expression of Fas-L mRNA in cells from non-lymphopenic patients compared with patients with advanced disease and healthy controls. Since CD4+ cells of Th1 phenotype are impaired during HIV-1 infection and show high cellular expression of Fas-L, it is conceivable that excess Fas-L during the early or non-lymphopenic phase of the disease increases the extent of apoptosis in these cells by the Fas/Fas-L pathway. The defective expression of the ligand in severely lymphopenic stages could be explained by exhaustion of this mechanism as the disease progresses.

Keywords: JOURNAL ARTICLE Antigens, CD95/ANALYSIS/GENETICS Apoptosis/IMMUNOLOGY Biological Markers CD4-Positive T-Lymphocytes/CHEMISTRY/CYTOLOGY/*VIROLOGY DNA Primers Flow Cytometry Gene Expression/IMMUNOLOGY Human HIV Infections/*IMMUNOLOGY/METABOLISM *HIV-1 Immunophenotyping Interferon Type II/ANALYSIS Linear Models Lymphopenia/*IMMUNOLOGY/METABOLISM/VIROLOGY Membrane Glycoproteins/ANALYSIS/*GENETICS Polymerase Chain Reaction RNA, Messenger/ANALYSIS Support, Non-U.S. Gov't
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A9950393

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