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Título: | Antigen-induced clustering of surface CD38 and recruitment of intracellular CD38 to the immunologic synapse |
Autor: | Muñoz, P.; Mittelbrunn, M.; Fuente, Hortensia de la; Pérez-Martínez, M.; García-Pérez, A.; Ariza-Veguillas, A.; Malavasi, F.; Zubiaur, Mercedes CSIC ORCID ; Sánchez-Madrid, Francisco; Sancho, Jaime CSIC ORCID | Director: | Universidad de Granada | Fecha de publicación: | 2008 | Editor: | American Society of Hematology | Citación: | Blood 111: 3653- 3664 (2008) | Resumen: | During immunologic synapse (IS) formation, human CD38 redistributes to the contact area of T cell-antigen-presenting cell (APC) conjugates in an antigen- dependent manner. Confocal microscopy showed that CD38 preferentially accumulated along the contact zone, whereas CD3-ζ redistributed toward the central zone of the IS. APC conjugates with human T cells or B cells transiently expressing CD38-green fluorescent protein revealed the presence of 2 distinct pools of CD38, one localized at the cell membrane and the other in recycling endosomes. Both pools were recruited to the T/APC contact sites and required antigen-pulsed APCs. The process appeared more efficient in T cells than in APCs. CD38 was actively recruited at the IS of T cells by means of Lck-mediated signals. Overex- pression of CD38 in T cells increased the levels of antigen-induced intracellular calcium release. Opposite results were obtained by down-regulating surface CD38 expression by means of CD38 siRNA. CD38 blockade in influenza HA-specific T cells inhibited IL-2 and IFN-γ production, PKCe phosphorylation at Thr538, and PKC6 recruitment to the IS induced by antigen-pulsed APCs. These results reveal a new role for CD38 in modulating antigen-mediated T-cell responses during IS formation. © 2008 by The American Society of Hematology. | URI: | http://hdl.handle.net/10261/74118 | DOI: | Antigen-induced clustering of surface CD38 and recruitment of intracellular CD38 to the immunologic synapse | Identificadores: | issn: 0006-4971 |
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