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Blood, 15 July 2005, Vol. 106, No. 2, pp. 626-634. Prepublished online as a Blood First Edition Paper on April 7, 2005; DOI 10.1182/blood-2004-05-2051. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: 2004-05-2051v1 106/2/626    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 ROSSI PACCANI, S. Articles by BALDARI, C. T Search for Related Content PubMed PubMed Citation Articles by ROSSI PACCANI, S. Articles by BALDARI, C. T Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted June 10, 2004 Accepted March 29, 2005 Defective VAV expression and impaired F-actin reorganization in a subset of common variable immunodeficiency patients with T-cell defects Silvia ROSSI PACCANI, Marianna BONCRISTIANO, Laura PATRUSSI, Cristina ULIVIERI, Andreas WACK, Silvia VALENSIN, Tim R HIRST, Amedeo AMEDEI, Gianfranco DEL PRETE, John L TELFORD, Mario M D'ELIOS, and Cosima T BALDARI* Department of Evolutionary Biology, University of Siena, Siena, Italy School of Molecular & Microbial Biosciences, The University of Sydney, Sidney, Australia Department of Internal Medicine and Immunoallergology, University of Florence, Florence, Italy Chiron Research Center, Siena, Italy * Corresponding author; email: baldari{at}unisi.it. Common variable immunodeficiency (CVID) is a primary immune disorder characterized by impaired antibody production, which is in many instances secondary to defective T-cell function (T-CVID). We have previously identified a subset of T-CVID patients characterized by defective TCR-dependent protein tyrosine phosphorylation. In these patients ZAP-70 fails to be recruited to the TCR as the result of impaired CD3 phosphorylation, which is however not dependent on defective Lck expression or activity. Here we show that neither Fyn or CD45 are affected in these patients. On the other hand, T-CVID T-cells show dramatic defects in the Vav/Rac pathway controlling F-actin dynamics. A significant deficiency in Vav protein was indeed observed, which in three out of four T-CVID patients was associated with reduced Vav1 mRNA levels. The impairment in Vav expression correlated with defective F-actin reorganization in response to TCR/CD28 coengagement. Furthermore, TCR/CD28 dependent upregulation of lipid rafts at the cell surface, which requires F-actin dynamics, was impaired in these patients. The actin cytoskeleton defect could be reversed by reconstitution of Vav1 expression in the patients' T-cells. The results provide the demonstration of an essential role of Vav in human T-cells and strongly suggest Vav insufficiency in T-CVID. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Patrussi, C. Ulivieri, O. M. Lucherini, S. R. Paccani, A. Gamberucci, L. Lanfrancone, P. G. Pelicci, and C. T. Baldari p52Shc is required for CXCR4-dependent signaling and chemotaxis in T cells Blood, September 15, 2007; 110(6): 1730 - 1738. [Abstract] [Full Text] [PDF] G. M. Fuhler, N. R. Blom, P. J. Coffer, A. L. Drayer, and E. Vellenga The reduced GM-CSF priming of ROS production in granulocytes from patients with myelodysplasia is associated with an impaired lipid raft formation J. Leukoc. Biol., February 1, 2007; 81(2): 449 - 457. [Abstract] [Full Text] [PDF] L. D. Finkelstein, Y. Shimizu, and P. L. Schwartzberg Tec Kinases Regulate TCR-Mediated Recruitment of Signaling Molecules and Integrin-Dependent Cell Adhesion J. Immunol., November 1, 2005; 175(9): 5923 - 5930. [Abstract] [Full Text] [PDF]

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