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  • Opinion
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The reverse stop-signal model for CTLA4 function

Abstract

Activation of the T-cell co-receptor cytotoxic T-lymphocyte antigen 4 (CTLA4) has a pivotal role in adjusting the threshold for T-cell activation and in preventing autoimmunity and massive tissue infiltration by T cells. Although many mechanistic models have been postulated, no single model has yet accounted for its overall function. In this Opinion article, I outline the strengths and weaknesses of the current models, and present a new 'reverse stop-signal model' to account for CTLA4 function.

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Figure 1: Cell-extrinsic models of CTLA4 function: cell-extrinsic factors may contribute to the hyper-lymphoproliferation phenotype of CTLA4-deficient mice.
Figure 2: Cell-intrinsic models of CTLA4 function: cell-intrinsic factors contribute to the function of T cells from CTLA4-deficient mice.
Figure 3: The 'reverse stop-signal' model.

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Acknowledgements

C.E.R is a Principal Research Fellow of the Wellcome Trust.

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Rudd, C. The reverse stop-signal model for CTLA4 function. Nat Rev Immunol 8, 153–160 (2008). https://doi.org/10.1038/nri2253

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