Damping by Depletion

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Science  29 Apr 2011:
Vol. 332, Issue 6029, pp. 542-543
DOI: 10.1126/science.1206122

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Superfluous or misguided human immune responses may lead to harmful outcomes, as seen in autoimmune disease and allergy, but the immune system has evolved mechanisms to suppress these reactions. One of the key molecules engaged in such suppressive control is cytotoxic T lymphocyte antigen–4 [(CTLA-4); also called CD152] (1). The molecule is expressed by certain T cell subpopulations, and animals lacking CTLA-4 die prematurely from massive T cell proliferation and severe autoimmunity (24). It has not been clear how CTLA-4 negatively controls immune responses via these T cells, but on page 600 of this issue, Qureshi et al. (5) report a mechanism by which the molecule modulates the function of antigen-presenting cells (such as dendritic cells) to control immunological self-tolerance and homeostasis.