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The reverse stop-signal model for CTLA4 function

Nature Reviews Immunology volume 8, pages 153–160 (2008)Cite this article

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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  1. Division of Immunology, Department of Pathology, Christopher E. Rudd is at the Cell Signalling Section, Tennis Court Road, CB1 4QP Cambridge, UK,

    Christopher E. Rudd

  2. Cambridge Institute for Medical Research, Hills Road, CB2 0XY Cambridge, UK.,

    Christopher E. Rudd

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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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