The DOI matches its Crossref record; 136 of the 136 references it cites were found in a registry or an index.
Treg and CTLA-4: Two intertwining pathways to immune tolerance
Open accessAbstract
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.
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Cites
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Metadata
- Authors
- Walker, L. S. K.
- Venue
- Journal of Autoimmunity
- Publisher
- Elsevier BV
- Published
- 2013-09
- Volume
- 45
- Pages
- 49-57
- ISSN
- 0896-8411 (ISSN-L)
- OpenAlex
- W1977144608
- Cited by
- 411
- References
- 136
- FWCI
- 11.64
- Type
- journal article
- Language
- en
- Open access
- hybrid
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