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Blood, 1 April 2008, Vol. 111, No. 7, pp. 3653-3664. Prepublished online as a Blood First Edition Paper on January 22, 2008; DOI 10.1182/blood-2007-07-101600. This Article Full Text (PDF) Supplemental Methods, Figure, and Video All Versions of this Article: blood-2007-07-101600v1 111/7/3653    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Munoz, P. Articles by Sancho, J. Search for Related Content PubMed PubMed Citation Articles by Munoz, P. Articles by Sancho, J. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted July 19, 2007 Accepted January 8, 2008 Antigen-induced clustering of surface CD38 and recruitment of intracellular CD38 to the immunological synapse Pilar Munoz, Maria Mittelbrunn, Hortensia de la Fuente, Manuel Perez-Martinez, Angelica Garcia-Perez, Adriana Ariza-Veguillas, Fabio Malavasi, Mercedes Zubiaur, Francisco Sanchez-Madrid, and Jaime Sancho* Departamento de Biologia Celular e Inmunologia, Instituto de Parasitologia y Biomedicina, "Lopez-Neyra", Consejo Superior de Investigaciones Cientificas, Armilla, Spain Departamento de Biologia Vascular e Inflamacion, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain Servicio de Inmunologia, Hospital Universitario de la Princesa, Universidad Autonoma de Madrid, Madrid, Spain Laboratory of Immunogenetics, University of Torino Medical School and CeRMS, Torino, Italy Instituto de Salud Carlos III, Majadahonda, Spain * Corresponding author; email: granada{at}ipb.csic.es. During immune synapse (IS) formation human CD38 redistributed to the contact area of T cell-APC conjugates in antigen-dependent manner. Confocal microscopy showed that CD38 preferentially accumulated along the contact zone, whereas CD3- 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 two distinct pools of CD38, one at the cell-membrane and the other one in recycling endosomes. Both pools were recruited to the T cell: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 mechanisms involving Lck-mediated signals. Over-expression of CD38 in T cells increased the levels of antigen-induced intracellular calcium release. Opposite results were obtained by down-regulating CD38 expression by means of CD38 siRNA. CD38 blockade in influenza HA-specific T cells inhibited IL-2, and IFN- production, PKC phosphorylation at Thr538, and PKC 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Koch-Nolte, F. Haag, A. H. Guse, F. Lund, and M. Ziegler Emerging Roles of NAD+ and Its Metabolites in Cell Signaling Sci. Signal., February 10, 2009; 2(57): mr1 - mr1. [Abstract] [Full Text] [PDF] F. Malavasi, S. Deaglio, A. Funaro, E. Ferrero, A. L. Horenstein, E. Ortolan, T. Vaisitti, and S. Aydin Evolution and Function of the ADP Ribosyl Cyclase/CD38 Gene Family in Physiology and Pathology Physiol Rev, July 1, 2008; 88(3): 841 - 886. [Abstract] [Full Text] [PDF]

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