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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 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 Citation Map 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 Muñoz, P. Articles by Sancho, J. Search for Related Content PubMed PubMed Citation Articles by Muñoz, P. Articles by Sancho, J. Related Collections Immunobiology Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  IMMUNOBIOLOGY Antigen-induced clustering of surface CD38 and recruitment of intracellular CD38 to the immunologic synapse Pilar Muñoz1, María Mittelbrunn2, Hortensia de la Fuente3, Manuel Pérez-Martínez3, Angélica García-Pérez1, Adriana Ariza-Veguillas1, Fabio Malavasi4, Mercedes Zubiaur1,5, Francisco Sánchez-Madrid2,3, and Jaime Sancho1 1 Departamento de Biología Celular e Inmunología, Instituto de Parasitología y Biomedicina "López-Neyra," Consejo Superior de Investigaciones Científicas, Armilla, Spain; 2 Departamento de Biología Vascular e Inflamación, Centro Nacional de Investigaciones Cardiovasculares, Madrid, Spain; 3 Servicio de Inmunología, Hospital Universitario de la Princesa, Universidad Autónoma de Madrid, Spain; 4 Laboratory of Immunogenetics, University of Torino Medical School and Centro di Ricerca in Medicina Sperimentale, Torino, Italy; and 5 Instituto de Salud Carlos III, Madrid, Spain 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- 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- 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. 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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