T-lymphocyte trafficking is targeted to specific organs by selective molecular interactions depending on their differentiation and functional properties. Specific chemokine receptors have been associated with organ-specific trafficking of memory and effector T-cells, as well as the recirculation of naïve T-cells to secondary lymphoid organs. In addition to the acquisition of tissue-selective integrins and chemokine receptors, an additional level of specificity for T-cell trafficking into the tissue is provided by specific recognition of antigen displayed by the endothelium involving the TCRs (T-cell antigen receptors) and co-stimulatory receptors. Activation of PI3K (phosphoinositide 3-kinase) is a robust signalling event shared by most chemokine receptors as well as the TCR and co-stimulatory receptors, contributing to several aspects of T-lymphocyte homing as well as actin reorganization and other components of the general migratory machinery. Accordingly, inhibition of PI3K has been considered seriously as a potential therapeutic strategy by which to combat various T-lymphocyte-dependent pathologies, including autoimmune and inflammatory diseases, as well as to prevent transplant rejection. However, there is substantial evidence for PI3K-independent mechanisms that facilitate T-lymphocyte migration. In this regard, several other signalling-pathway components, including small GTPases, PLC (phospholipase C) and PKC (protein kinase C) isoforms, have also been implicated in T-lymphocyte migration in response to chemokine stimulation. The present review will therefore examine the PI3K-dependent and -independent signal-transduction pathways involved in T-cell migration during distinct modes of T-cell trafficking in response to either chemokines or the TCR and co-stimulatory molecules.
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February 2009
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Review Article|
January 28 2009
Mechanisms of chemokine and antigen-dependent T-lymphocyte navigation
Stephen G. Ward;
Stephen G. Ward
1
*Department of Pharmacy and Pharmacology, University of Bath, Claverton Down, Bath BA2 7AY, U.K.
1To whom correspondence should be addressed (email [email protected]).
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Federica M. Marelli-Berg
Federica M. Marelli-Berg
†Department of Immunology, Division of Medicine, Imperial College London, Du Cane Road, London W12 0NN, U.K.
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Publisher: Portland Press Ltd
Received:
October 02 2008
Revision Received:
November 06 2008
Accepted:
November 06 2008
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© The Authors Journal compilation © 2009 Biochemical Society
2009
Biochem J (2009) 418 (1): 13–27.
Article history
Received:
October 02 2008
Revision Received:
November 06 2008
Accepted:
November 06 2008
Citation
Stephen G. Ward, Federica M. Marelli-Berg; Mechanisms of chemokine and antigen-dependent T-lymphocyte navigation. Biochem J 15 February 2009; 418 (1): 13–27. doi: https://doi.org/10.1042/BJ20081969
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