Role of CD95-activated caspase-1 processing of IL-1β in TCR-mediated proliferation of HIV-infected CD4+ T cells

✍ Scribed by Frédéric Petit; Jacques Corbeil; Jean-Daniel Lelièvre; Laure Moutouh-de Parseval; Grégory Pinon; Douglas R. Green; Jean Claude Ameisen; Jérôme Estaquier

• Publisher: John Wiley and Sons
• Year: 2001
• Tongue: English
• Weight: 323 KB
• Volume: 31
• Category: Article
• ISSN: 0014-2980
• DOI: 10.1002/1521-4141(200112)31:12<3513::aid-immu3513>3.0.co;2-j

✦ Synopsis

CD95 plays a critical role in the homeostasis of the immune system, and has been reported to participate in T cell death during HIV infection. Here we report that the response to CD3-TCR stimulation of CD4 + T cells from HIV-infected individuals and CD4 + T cells from healthy donors incubated in vitro with HIV-1 Lai depends on the manner the CD3-TCR complex is engaged. While stimulation by anti-CD3 antibodies in solution induced CD4 T cell apoptosis both in the absence or presence of anti-CD95 antibodies, stimulation by immobilized anti-CD3 antibodies rendered CD4 + T cells resistant to CD95-mediated death and led to increased CD4 T cell proliferation in response to CD95 ligation. CD95 ligation of CD4 + T cells led to the activation of caspases, while costimulation induced by anti-CD3 and anti-CD95 mAb prevented the full processing of caspase-3 and caspase-8. Proliferation of CD4 + T cells induced by CD3-TCR and CD95 costimulation was decreased by treatments with a caspase-1 inhibitor or with neutralizing antibodies to IL-1ß, indicating a requirement for caspase-1-mediated IL-1 g processing and secretion. Our findings suggest a novel mechanism whereby in addition to its role in inducing T cell apoptosis, CD95 signaling during HIV infection may also provide a costimulatory signal leading to an enhancement of CD4 T cell proliferation in response to CD3-TCR complex engagement.