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Department of Microbiology and Immunology, University of Miami School of Medicine, Miami, FL 33136
The importance of IL-2Rß function for immune regulation is
highlighted by the severe impairment in lymphoid cell function in
IL-2Rß-deficient mice. It has been speculated that failed IL-2/IL-2R
signaling in peripheral T cells causes the associated autoimmunity,
imbalanced peripheral lymphoid homeostasis, and defective T cell
function. This study explored the requirement for IL-2Rß function in
mature T lymphocytes. We show that transgenic thymic expression of the
IL-2R ß-chain in IL-2Rß-deficient mice prevents lethal
autoimmunity, restores normal production of B lymphocytes, and results
in a peripheral T cell compartment that is responsive to triggering
through the TCR, but not the IL-2R. The dysfunction of the IL-2R is
illustrated by the near complete failure of mature T cells to
proliferate to IL-2 in vitro and in vivo, to differentiate into CTL,
and to up-regulate IL-2R
expression. These data indicate that
lymphoid homeostasis is largely maintained despite a nonfunctional
IL-2R in mature T lymphocytes and suggest that IL-2Rß provides an
essential signal during thymic development to regulate
self-reactivity.
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