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Science 1 March 1996:
Vol. 271. no. 5253, pp. 1272 - 1276
DOI: 10.1126/science.271.5253.1272
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Reports

Blocked Signal Transduction to the ERK and JNK Protein Kinases in Anergic CD4+ T Cells

Wei Li, Carmella D. Whaley, Anna Mondino, Daniel L. Mueller *

T cells activated by antigen receptor stimulation in the absence of accessory cell-derived costimulatory signals lose the capacity to synthesize the growth factor interleukin-2 (IL-2), a state called clonal anergy. An analysis of CD3- and CD28-induced signal transduction revealed reduced ERK and JNK enzyme activities in murine anergic T cells. The amounts of ERK and JNK proteins were unchanged, and the kinases could be fully activated in the presence of phorbol 12-myristate 13-acetate. Dephosphorylation of the calcineurin substrate NFATp (preexisting nuclear factor of activated T cells) also remained inducible. These results suggest that a specific block in the activation of ERK and JNK contributes to defective IL-2 production in clonal anergy.

W. Li, C. D. Whaley, D. L. Mueller, Department of Medicine and Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
A. Mondino, Department of Microbiology and Center for Immunology, University of Minnesota Medical School, Minneapolis, MN 55455, USA.
* To whom correspondence should be addressed.


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T Cell Effector Function and Anergy Avoidance Are Quantitatively Linked to Cell Division.
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J. Immunol. 165, 2432-2443
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Repression of IL-2 Promoter Activity by the Novel Basic Leucine Zipper p21SNFT Protein.
M. Iacobelli, W. Wachsman, and K. L. McGuire (2000)
J. Immunol. 165, 860-868
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The Duration of Nuclear Residence of NFAT Determines the Pattern of Cytokine Expression in Human SCID T Cells.
S. Feske, R. Draeger, H.-H. Peter, K. Eichmann, and A. Rao (2000)
J. Immunol. 165, 297-305
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Impaired Ca/calcineurin pathway in in vivo anergized CD4 T cells.
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   Abstract »    Full Text »    PDF »
The -180 Site of the IL-2 Promoter Is the Target of CREB/CREM Binding in T Cell Anergy.
J. D. Powell, C. G. Lerner, G. R. Ewoldt, and R. H. Schwartz (1999)
J. Immunol. 163, 6631-6639
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Increased c-Fos/activator protein-1 confers resistance against anergy induction on antigen-specific T cell.
H. Kawasaki1, Y. Nakata, G. Suzuki, K. Chihara, T. Tokuhisa, and S. Shiozawa (1999)
Int. Immunol. 11, 1873-1880
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Sustained Activation of the Raf-MEK-ERK Pathway Elicits Cytokine Unresponsiveness in T Cells.
D. Chen, V. Heath, A. O'Garra, J. Johnston, and M. McMahon (1999)
J. Immunol. 163, 5796-5805
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Antigen-Experienced T Cells Undergo a Transient Phase of Unresponsiveness Following Optimal Stimulation.
F. De Mattia, S. Chomez, F. Van Laethem, V. Moulin, J. Urbain, M. Moser, O. Leo, and F. Andris (1999)
J. Immunol. 163, 5929-5936
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Intranasal Exposure to Protein Antigen Induces Immunological Tolerance Mediated by Functionally Disabled CD4+ T Cells.
D. C. Tsitoura, R. H. DeKruyff, J. R. Lamb, and D. T. Umetsu (1999)
J. Immunol. 163, 2592-2600
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