The role of interleukin-converting enzyme in Fas-mediated apoptosis in HIV-1 infection

The Journal of Clinical Investigation
E M SloandN S Young

Abstract

Apoptosis of CD4+ lymphocytes is partially responsible for the depletion of these cells in HIV-infected individuals. CD4+ lymphocytes from HIV-1-infected patients express higher membrane levels of the Fas receptor, and are particularly susceptible to apoptosis after Fas triggering. IL-1beta- converting enzyme (ICE) is a key enzyme of the apoptotic machinery involved in Fas-mediated apoptosis of normal lymphocytes. The role of ICE in mediating the increased susceptibility of CD4+ lymphocytes from HIV-1-infected patients to apoptosis has not been examined. In this study, we found that ICE mRNA was present in T cells from both HIV-1-infected patients and controls. Active ICE proteins, p10 and p20, were demonstrated by immunoblot in lymphocytes from HIV-1-infected patients and in normal lymphocytes after treatment with Fas agonist, CH11 mAb. Cocultivation of lymphocytes from HIV-1-infected persons with Fas antagonist, antibody ZB4, resulted in decreased expression of ICE protein in lymphocytes from HIV-infected patients, and decreased apoptosis. Similar effects were obtained when cells were treated with synthetic ICE inhibitors, which blocked apoptosis in response to Fas triggering. When CD4+ and CD8+ cells were sorted by flow cyto...Continue Reading

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Citations

Mar 18, 2003·International Immunopharmacology·A WanchuS Singh
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Dec 14, 2019·Molecular Immunology·Vinicius Nunes Cordeiro LealAlessandra Pontillo

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis