Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (14)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Rivero-Carmena, M.
Right arrow Articles by Regueiro, J. R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rivero-Carmena, M.
Right arrow Articles by Regueiro, J. R.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

International Immunology, Vol. 12, No. 6, 927-935, June 2000
© 2000 Japanese Society for Immunology

Membrane and transmembrane signaling in Herpesvirus saimiri-transformed human CD4+ and CD8+ T lymphocytes is ATM-independent.

Miguel Rivero-Carmena, Oscar Porras1, Blondineth Pelaez, Alberto Pacheco-Castro, Richard A. Gatti2 and José R. Regueiro

Inmunología, Facultad de Medicina, Universidad Complutense, 28040 Madrid, Spain
1 Inmunología, Hospital Nacional de Niños, San José, Costa Rica
2 Department of Pathology, University of California at Los Angeles School of Medicine, Los Angeles, CA 90095-1732, USA

Correspondence to: J. R. Regueiro

In the genetic disorder ataxia telangiectasia (AT), humoral (B) and cellular (T) immunological abnormalities are frequently observed. As a consequence, AT patients are predisposed to life-threatening sinopulmonary infections. The pathogenic mechanisms remain unknown, but a role for ATM in signal transduction from membrane receptors has been proposed. We have explored the effects of a defective ATMgene on isolated human T-lineage cells from 13 AT patients with proven T cell dysfunction by transforming their CD4+ and CD8+ T lymphocytes with Herpesvirus saimiri, and analyzing their signaling behavior as compared to normal controls. Several functional parameters were assayed in response to both membrane (anti-CD3 and IL-2) and transmembrane (phorbol myristate acetate plus the calcium ionophore ionomycin) stimuli: (i) calcium mobilization, (ii) induction of activation molecules (CD25, CD40 ligand, CD69 and CD71), (iii) cytokine synthesis (IL-2 and tumor necrosis factor-{alpha}) and (iv) proliferation. All these early and late activation events were found to be normal in the transformed ATM–/–T cells, indicating that ATM is not necessary for their induction. As expected, ATM–/– transformed T cells showed an increased radiosensitivity by both radioresistant DNA synthesis and cell survival assays. In contrast to an earlier report testing transformed B lymphocytes, our results indicate that transformed mature peripheral T lymphocytes from AT patients do not have intrinsic immune function defects. Rather, the described T-lineage signaling impairments observed in patients may be secondary in vivo to extrinsic ATM-dependent suppressive factors and/or to a developmental defect. These transformed T cells may help to understand the distinct biological role of ATM in different cell types and to develop rational therapies for the immunological dysfunction of AT patients.

Keywords: ATM protein, ataxia telangiectasia, Herpesvirus saimiri-transformed human T cells, T cell signaling

Transmitting editor: T. Saito


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J. Leukoc. Biol.Home page
J. M. Martin-Fernandez, J. A. Cabanillas, M. Rivero-Carmena, E. Lacasa, J. Pardo, A. Anel, P. R. Ramirez-Duque, F. Merino, C. Rodriguez-Gallego, and J. R. Regueiro
Herpesvirus saimiri-transformed CD8+ T cells as a tool to study Chediak-Higashi syndrome cytolytic lymphocytes
J. Leukoc. Biol., May 1, 2005; 77(5): 661 - 668.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.