Lymphoproliferative Disorders with Early Lethality in Mice Deficient in Ctla-4

P Waterhouse, JM Penninger, E Timms, A Wakeham… - Science, 1995 - science.org
P Waterhouse, JM Penninger, E Timms, A Wakeham, A Shahinian, KP Lee, CB Thompson
Science, 1995science.org
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 …
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.
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