Antigen-induced clustering of surface CD38 and recruitment of intracellular CD38 to the immunologic synapse

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 ce...

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Veröffentlicht in:Blood 2008-04, Vol.111 (7), p.3653-3664
Hauptverfasser: Muñoz, Pilar, Mittelbrunn, María, de la Fuente, Hortensia, Pérez-Martínez, Manuel, García-Pérez, Angélica, Ariza-Veguillas, Adriana, Malavasi, Fabio, Zubiaur, Mercedes, Sánchez-Madrid, Francisco, Sancho, Jaime
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Sprache:eng
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Zusammenfassung: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. Overexpression 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, PKCθ phosphorylation at Thr538, and PKCθ 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.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2007-07-101600