NDLI: T-cell anergy and peripheral T-cell tolerance.

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T-cell anergy and peripheral T-cell tolerance.

Content Provider	PubMed Central
Author	Lechler, R. Chai, J. G. Marelli-berg, F. Lombardi, G.
Abstract	The discovery that T-cell recognition of antigen can have distinct outcomes has advanced understanding of peripheral T-cell tolerance, and opened up new possibilities in immunotherapy. Anergy is one such outcome, and results from partial T-cell activation. This can arise either due to subtle alteration of the antigen, leading to a lower-affinity cognate interaction, or due to a lack of adequate co-stimulation. The signalling defects in anergic T cells are partially defined, and suggest that T-cell receptor (TCR) proximal, as well as downstream defects negatively regulate the anergic T cell's ability to be activated. Most importantly, the use of TCR-transgenic mice has provided compelling evidence that anergy is an in vivo phenomenon, and not merely an in vitro artefact. These findings raise the question as to whether anergic T cells have any biological function. Studies in rodents and in man suggest that anergic T cells acquire regulatory properties; the regulatory effects of anergic T cells require cell to cell contact, and appear to be mediated by inhibition of antigen-presenting cell immunogenicity. Close similarities exist between anergic T cells, and the recently defined CD4+ CD25+ population of spontaneously arising regulatory cells that serve to inhibit autoimmunity in mice. Taken together, these findings suggest that a spectrum of regulatory T cells exists. At one end of the spectrum are cells, such as anergic and CD4+ CD25+ T cells, which regulate via cell-to-cell contact. At the other end of the spectrum are cells which secrete antiinflammatory cytokines such as interleukin 10 and transforming growth factor-beta. The challenge is to devise strategies that reliably induce T-cell anergy in vivo, as a means of inhibiting immunity to allo- and autoantigens.
Related Links	http://dx.doi.org/10.1098/rstb.2001.0844
Ending Page	637
Page Count	13
Starting Page	625
File Format	PDF
ISSN	09628436
e-ISSN	14712970
Journal	Philosophical Transactions of the Royal Society of London. Series B
Issue Number	1409
Volume Number	356
Language	English
Publisher Date	2001-05-29
Access Restriction	Open
Subject Keyword	Biochemistry, Genetics and Molecular Biology(all) Agricultural and Biological Sciences(all) Research in Higher Education
Content Type	Text
Resource Type	Article
Subject	Biochemistry, Genetics and Molecular Biology Agricultural and Biological Sciences

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