Walker, LS;
(2013)
Treg and CTLA-4: Two intertwining pathways to immune tolerance.
J Autoimmun
, 45
pp. 49-57.
10.1016/j.jaut.2013.06.006.
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Abstract
Both the CTLA-4 pathway and regulatory T cells (Treg) are essential for the control of immune homeostasis. Their therapeutic relevance is highlighted by the increasing use of anti-CTLA-4 antibody in tumor therapy and the development of Treg cell transfer strategies for use in autoimmunity and transplantation settings. The CTLA-4 pathway first came to the attention of the immunological community in 1995 with the discovery that mice deficient in Ctla-4 suffered a fatal lymphoproliferative syndrome. Eight years later, mice lacking the critical Treg transcription factor Foxp3 were shown to exhibit a remarkably similar phenotype. Much of the debate since has centered on the question of whether Treg suppressive function requires CTLA-4. The finding that it does in some settings but not in others has provoked controversy and inevitable polarization of opinion. In this article, I suggest that CTLA-4 and Treg represent complementary and largely overlapping mechanisms of immune tolerance. I argue that Treg commonly use CTLA-4 to effect suppression, however CTLA-4 can also function in the non-Treg compartment while Treg can invoke CTLA-4-independent mechanisms of suppression. The notion that Foxp3 and CTLA-4 direct independent programs of immune regulation, which in practice overlap to a significant extent, will hopefully help move us towards a better appreciation of the underlying biology and therapeutic significance of these pathways.
Type: | Article |
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Title: | Treg and CTLA-4: Two intertwining pathways to immune tolerance. |
Open access status: | An open access version is available from UCL Discovery |
DOI: | 10.1016/j.jaut.2013.06.006 |
Publisher version: | http://dx.doi.org/10.1016/j.jaut.2013.06.006 |
Additional information: | �© 2013 Elsevier Ltd. All rights reserved. This work is licensed under a Creative Commons Attribution 3.0 Unported License. |
Keywords: | CD4 T cells, CTLA-4, Foxp3, Immune regulation, Tolerance, Treg |
UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Infection and Immunity |
URI: | https://discovery.ucl.ac.uk/id/eprint/1400065 |
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