HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yu, X.-Z. Articles by Anasetti, C. Search for Related Content PubMed PubMed Citation Articles by Yu, X.-Z. Articles by Anasetti, C.

Lck Is Required for Activation-Induced T Cell Death after TCR Ligation with Partial Agonists¹

Xue-Zhong Yu^2,*,, Steven D. Levin^3,, Joaquin Madrenas and Claudio Anasetti^*,

^* Human Immunogenetics Program, Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98109; Departments of Immunology and Medicine, University of Washington, Seattle, WA 98195; and Departments of Microbiology and Immunology, and Medicine, University of Western Ontario, and the John P. Robarts Institute, London, Ontario, Canada.

TCR engagement can induce either T cell proliferation and differentiation or activation-induced T cell death (AICD) through apoptosis. The intracellular signaling pathways that dictate such a disparate fate after TCR engagement have only been partially elucidated. Non-FcR-binding anti-CD3 mAbs induce a partial agonist TCR signaling pattern and cause AICD on Ag-activated, cycling T cells. In this study, we examined TCR signaling during the induction of AICD by anti-CD3 fos, a non-FcR-binding anti-CD3 mAb. This mAb activates Fyn, Lck, and extracellular signal-regulated kinase, and induces phosphorylation of Src-like adapter protein, despite the inability to cause calcium mobilization or TCR polarization. Anti-CD3 fos also fails to effectively activate -associated protein of 70 kDa or NF-B. Using Ag-specific T cells deficient for Fyn or Lck, we provide compelling evidence that activation of Lck is required for the induction of AICD. Our data indicate that a selective and distinct TCR signaling pattern is required for AICD by TCR partial agonist ligands.

This article has been cited by other articles:

				R. Weichsel, C. Dix, L. Wooldridge, M. Clement, A. Fenton-May, A. K. Sewell, J. Zezula, E. Greiner, E. Gostick, D. A. Price, et al. Profound Inhibition of Antigen-Specific T-Cell Effector Functions by Dasatinib Clin. Cancer Res., April 15, 2008; 14(8): 2484 - 2491. [Abstract] [Full Text] [PDF]

				P. A. Efron, A. Martins, D. Minnich, K. Tinsley, R. Ungaro, F. R. Bahjat, R. Hotchkiss, M. Clare-Salzler, and L. L. Moldawer Characterization of the Systemic Loss of Dendritic Cells in Murine Lymph Nodes During Polymicrobial Sepsis J. Immunol., September 1, 2004; 173(5): 3035 - 3043. [Abstract] [Full Text] [PDF]