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Cutting Edge: Modulation of Fas-Mediated Apoptosis by Lipid Rafts in T Lymphocytes¹

Patrick Legembre^2,*, Sophie Daburon^*, Patrick Moreau, Jean-François Moreau^* and Jean-Luc Taupin^*

^* Laboratoire Composantes Innées de la Réponse Immunitaire et Différenciation, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5164 and Laboratoire de Biogenèse Membranaire, Centre National de la Recherche Scientifique Unité Mixte de Recherche 5200, University of Bordeaux 2, Bordeaux, France

In type I cells, Fas-mediated cell death requires cytoplasmic membrane subdomains called microdomains or lipid rafts. On the contrary, Fas signaling is independent of these structures in type II cells. We report that in human T cells, CD28, CD59, and CD55 are all localized into lipid rafts and that CD28 is concentrated into microdomains enriched in ganglioside GM1, whereas CD59 and CD55 are not. Moreover, CD28 cross-linking leads to the formation of lipid raft clusters which exclude CD59 and CD55, and reciprocally. Coligation of Fas with CD55 or CD59 inhibits the apoptotic signal, whereas CD28 recruitment amplifies the Fas signaling pathway. Therefore, we conclude that 1) different types of microdomains exist on the cell surface, with distinct functional properties and 2) the recruitment of these distinct structures may differentially modulate the Fas pathway. Moreover, our results demonstrate that Fas-induced apoptosis can be controlled at the level of the cytoplasmic membrane.

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