Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

Eµ-TCL1 Mice Represent a Model for Immunotherapeutic Reversal of Chronic Lymphocytic Leukemia-Induced T-Cell Dysfunction

Gullu Gorgun, Alan G. Ramsay, Tobias A. W. Holderried, David Zahrieh, Rifca Le Dieu, Fenglong Liu, John Quackenbush, Carlo M. Croce, John G. Gribben and Carlo M. Croce
Proceedings of the National Academy of Sciences of the United States of America
Vol. 106, No. 15 (Apr. 14, 2009), pp. 6250-6255
Stable URL: http://www.jstor.org/stable/40482076
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
Eµ-TCL1 Mice Represent a Model for Immunotherapeutic Reversal of Chronic Lymphocytic Leukemia-Induced T-Cell Dysfunction
Preview not available

Abstract

Preclinical animal models have largely ignored the immune-suppressive mechanisms that are important in human cancers. The identification and use of such models should allow better predictions of successful human responses to immunotherapy. As a model for changes induced in nonmalignant cells by cancer, we examined T-cell function in the chronic lymphocytic leukemia (CLL) Eμ-TCL1 transgenic mouse model. With development of leukemia, Eμ-TCL1 transgenic mice developed functional T-cell defects and alteration of gene and protein expression closely resembling changes seen in CLL human patients. Furthermore, infusion of CLL cells into young Eμ-TCL1 mice induced defects comparable to those seen in mice wjth developed leukemia, demonstrating a causal relationship between leukemia and the T-cell defects. Altered pathways involved genes regulating act in remodeling, and T cells exhibited dysfunctional immunological synapse formation and T-cell signaling, which was reversed by the immunomodulatory drug lenalidomide. These results further demonstrate the utility of this animal model of CLL and define a versatile model to investigate both the molecular mechanisms of cancer-induced immune suppression and immunotherapeutic repair strategies.

Page Thumbnails

  • Thumbnail: Page 
[6250]
    [6250]
  • Thumbnail: Page 
6251
    6251
  • Thumbnail: Page 
6252
    6252
  • Thumbnail: Page 
6253
    6253
  • Thumbnail: Page 
6254
    6254
  • Thumbnail: Page 
6255
    6255