Lymphoproliferative Disorders with Early Lethality in Mice Deficient in <i>Ctla-4</i>

DOI Web Site 86 Citations
  • Paul Waterhouse
    P. Waterhouse, J. M. Penninger, E. Timms, A. Wakeham, A. Shahinian, T. W. Mak, Amgen Institute, Ontario Cancer Institute, Departments of Immunology and Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2C1, Canada.
  • Josef M. Penninger
    P. Waterhouse, J. M. Penninger, E. Timms, A. Wakeham, A. Shahinian, T. W. Mak, Amgen Institute, Ontario Cancer Institute, Departments of Immunology and Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2C1, Canada.
  • Emma Timms
    P. Waterhouse, J. M. Penninger, E. Timms, A. Wakeham, A. Shahinian, T. W. Mak, Amgen Institute, Ontario Cancer Institute, Departments of Immunology and Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2C1, Canada.
  • Andrew Wakeham
    P. Waterhouse, J. M. Penninger, E. Timms, A. Wakeham, A. Shahinian, T. W. Mak, Amgen Institute, Ontario Cancer Institute, Departments of Immunology and Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2C1, Canada.
  • Arda Shahinian
    P. Waterhouse, J. M. Penninger, E. Timms, A. Wakeham, A. Shahinian, T. W. Mak, Amgen Institute, Ontario Cancer Institute, Departments of Immunology and Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2C1, Canada.
  • Kelvin P. Lee
    K. P. Lee and C. B. Thompson, Howard Hughes Medical Institute, Gwen Knapp Center, University of Chicago, Chicago, IL, 60637, USA.
  • Craig B. Thompson
    K. P. Lee and C. B. Thompson, Howard Hughes Medical Institute, Gwen Knapp Center, University of Chicago, Chicago, IL, 60637, USA.
  • Henrik Griesser
    H. Griesser, Department of Pathology, University of Toronto, Toronto, Ontario M5G 2C1, Canada.
  • Tak W. Mak
    P. Waterhouse, J. M. Penninger, E. Timms, A. Wakeham, A. Shahinian, T. W. Mak, Amgen Institute, Ontario Cancer Institute, Departments of Immunology and Medical Biophysics, University of Toronto, Toronto, Ontario M5G 2C1, Canada.

Description

<jats:p>The role of the cell-surface molecule CTLA-4 in the regulation of T cell activation has been controversial. Here, lymph nodes and spleens of CTLA-4-deficient mice accumulated T cell blasts with up-regulated activation markers. These blast cells also infiltrated liver, heart, lung, and pancreas tissue, and amounts of serum immunoglobulin were elevated. The mice invariably became moribund by 3 to 4 weeks of age. Although CTLA-4-deficient T cells proliferated spontaneously and strongly when stimulated through the T cell receptor, they were sensitive to cell death induced by cross-linking of the Fas receptor and by gamma irradiation. Thus, CTLA-4 acts as a negative regulator of T cell activation and is vital for the control of lymphocyte homeostasis.</jats:p>

Journal

  • Science

    Science 270 (5238), 985-988, 1995-11-10

    American Association for the Advancement of Science (AAAS)

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