Decreased function of Fas in patients displaying delayed progression of HIV-induced immune deficiency
| Autor: | Irma Dianzani, Sara Bonissoni, Manuela Bragardo, Donatella Buonfiglio, Daniela DiFranco, Roberto Cauda, Maria Rosaria Capobianchi, Caterina Mezzatesta, Flavia Bottarel, Thea Bensi, Claudia Balotta, Umberto Dianzani, M. B. Lucia |
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| Rok vydání: | 2000 |
| Předmět: |
Programmed cell death
medicine.drug_class T-Lymphocytes Apoptosis Biology Monoclonal antibody Settore MED/17 - MALATTIE INFETTIVE Asymptomatic HIV Long-Term Survivors Immune system Viral envelope medicine Humans fas Receptor Family Health Acquired Immunodeficiency Syndrome Antibodies Monoclonal Hematology FAS Prognosis immunological progression Cell culture Case-Control Studies Immunology Fas signaling pathway Disease Progression HIV/AIDS medicine.symptom Signal Transduction |
| Zdroj: | The hematology journal : the official journal of the European Haematology Association. 2(4) |
| ISSN: | 1466-4860 |
| Popis: | INTRODUCTION In acquired immune deficiency syndrome patients, apoptosis of uninfected lymphocytes may contribute to development of immune deficiency. This process may involve recruitment of Fas by human immunodeficiency virus products. In line with this possibility, the viral envelope glycoprotein gp120 does not induce death of T cells from subjects with the autoimmune/lymphoproliferative syndrome displaying defective Fas function. This study evaluates the possibility that Fas function defects delay progression of HIV-induced immune deficiency. MATERIALS AND METHODS The susceptibility to Fas-induced cell death was assessed on T cells from 18 'long-term non-progressor', four 'non-progressor', four 'progressor' asymptomatic HIV-1-infected, and nine AIDS patients using anti-Fas monoclonal antibodies. RESULTS Fas-induced cell death was significantly lower in long-term non-progressors and non-progressors than in normal controls, progressors, and AIDS. The single-patient data showed that 9/18 long-term non-progressors and 3/4 non-progressors, but no progressors or AIDS were resistant to Fas. Analysis of the uninfected parents of two long-term non-progressors displaying decreased Fas-function showed that the mother of one of them and the father of the other displayed the same Fas function defect as their children. Fusion of T cells from Fas-resistant individuals with a Fas-sensitive cell line gave rise to Fas-resistant hybrid lines not carrying HIV, which suggests that the resistant phenotype is due to molecules exerting a dominant negative effect on a normal Fas system. CONCLUSION These data suggest that Fas-resistance in long-term non-progressors may be due to inherited alterations of the Fas signaling pathway and may be a novel factor in delayed progression. |
| Databáze: | OpenAIRE |
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