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*
Committee on Immunology and
Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, IL 60637
LFA-1 is a well-recognized adhesion molecule, but its role in
providing costimulatory signals to T cells has remained controversial.
We have compared the ability of class II-positive transfectants that do
and do not coexpress ICAM-1 (ProAd and ProAd-ICAM) to activate
Ag-specific Th1 clones and naive CD4-positive T cells isolated from TCR
transgenic mice. Ag presentation by ProAd to Th1 clones can induce
calcium-dependent signaling events after engagement of the TCR, as
evidenced by the nuclear localization of the transcription factors
NF-AT and NF-
B. Nevertheless, coexpression of ICAM-1 or B7-1 on
ProAd is required to induce detectable levels of IL-2 gene expression
in either Th1 clones or naive T cells. In Th1 clones, activation by
ProAd-ICAM induces very transient IL-2 mRNA expression that does not
result in detectable IL-2 secretion or T cell proliferation. In naive T
cells, the duration of IL-2 mRNA expression is longer, allowing for a
transient burst of IL-2 protein that is sufficient to drive the cells
into the cell cycle. In spite of this initial response, Ag presentation
by ProAd-ICAM is a tolerogenic signal to naive T cells, and responding
T cells undergo apoptosis 4 to 5 days poststimulation. These data
suggest that engagement of LFA-1 can provide sufficient costimulatory
signals to induce T cell activation and IL-2 gene expression, but
cannot protect against anergy induction or provide for T cell survival.
This article has been cited by other articles:
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H. H. Smits, E. C. de Jong, J. H. N. Schuitemaker, T. B. H. Geijtenbeek, Y. van Kooyk, M. L. Kapsenberg, and E. A. Wierenga Intercellular Adhesion Molecule-1/LFA-1 Ligation Favors Human Th1 Development J. Immunol., February 15, 2002; 168(4): 1710 - 1716. [Abstract] [Full Text] [PDF]
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D. Bechard, A. Scherpereel, H. Hammad, T. Gentina, A. Tsicopoulos, M. Aumercier, J. Pestel, J.-P. Dessaint, A.-B. Tonnel, and P. Lassalle Human Endothelial-Cell Specific Molecule-1 Binds Directly to the Integrin CD11a/CD18 (LFA-1) and Blocks Binding to Intercellular Adhesion Molecule-1 J. Immunol., September 15, 2001; 167(6): 3099 - 3106. [Abstract] [Full Text] [PDF]
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H.-T. Ni, M. J. Deeths, and M. F. Mescher LFA-1-Mediated Costimulation of CD8+ T Cell Proliferation Requires Phosphatidylinositol 3-Kinase Activity J. Immunol., June 1, 2001; 166(11): 6523 - 6529. [Abstract] [Full Text] [PDF]
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 J. L. Ragazzo, M. E. Ozaki, L. Karlsson, P. A. Peterson, and S. R. Webb Costimulation via lymphocyte function-associated antigen 1 in the absence of CD28 ligation promotes anergy of naive CD4+ T cells PNAS, December 14, 2000; (2000) 11397798. [Abstract] [Full Text]
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S. A. Jenks and J. Miller Inhibition of IL-4 Responses After T Cell Priming in the Context of LFA-1 Costimulation Is Not Reversed by Restimulation in the Presence of CD28 Costimulation J. Immunol., January 1, 2000; 164(1): 72 - 78. [Abstract] [Full Text] [PDF]
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H.-M. Dosch, R. K. Cheung, W. Karges, M. Pietropaolo, and D. J. Becker Persistent T Cell Anergy in Human Type 1 Diabetes J. Immunol., December 15, 1999; 163(12): 6933 - 6940. [Abstract] [Full Text] [PDF]
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R. S. Liwski and T. D. G. Lee Nematode Infection Enhances Survival of Activated T Cells by Modulating Accessory Cell Function J. Immunol., November 1, 1999; 163(9): 5005 - 5012. [Abstract] [Full Text] [PDF]
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P. Bertolino, M.-C. Trescol-Biemont, J. Thomas, B. F. de St Groth, M. Pihlgren, J. Marvel, and C. Rabourdin-Combe Death by neglect as a deletional mechanism of peripheral tolerance Int. Immunol., August 1, 1999; 11(8): 1225 - 1238. [Abstract] [Full Text] [PDF]
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H.-T. Ni, M. J. Deeths, W. Li, D. L. Mueller, and M. F. Mescher Signaling Pathways Activated by Leukocyte Function-Associated Ag-1-Dependent Costimulation J. Immunol., May 1, 1999; 162(9): 5183 - 5189. [Abstract] [Full Text] [PDF]
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C. Abraham, J. Griffith, and J. Miller The Dependence for Leukocyte Function-Associated Antigen-1/ICAM-1 Interactions in T Cell Activation Cannot Be Overcome by Expression of High Density TCR Ligand J. Immunol., April 15, 1999; 162(8): 4399 - 4405. [Abstract] [Full Text] [PDF]
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C. E. Sedwick, M. M. Morgan, L. Jusino, J. L. Cannon, J. Miller, and J. K. Burkhardt TCR, LFA-1, and CD28 Play Unique and Complementary Roles in Signaling T Cell Cytoskeletal Reorganization J. Immunol., February 1, 1999; 162(3): 1367 - 1375. [Abstract] [Full Text] [PDF]
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J. L. Ragazzo, M. E. Ozaki, L. Karlsson, P. A. Peterson, and S. R. Webb Costimulation via lymphocyte function-associated antigen 1 in the absence of CD28 ligation promotes anergy of naive CD4+ T cells PNAS, January 2, 2001; 98(1): 241 - 246. [Abstract] [Full Text] [PDF]
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