UCL Discovery
UCL home » Library Services » Electronic resources » UCL Discovery

Treg and CTLA-4: Two intertwining pathways to immune tolerance.

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. Green open access

[thumbnail of 1-s2.0-S0896841113000802-main.pdf]
Preview
PDF
1-s2.0-S0896841113000802-main.pdf

Download (800kB)

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
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
Downloads since deposit
423Downloads
Download activity - last month
Download activity - last 12 months
Downloads by country - last 12 months

Archive Staff Only

View Item View Item