T cell affinity regulates asymmetric division, effector cell differentiation, and tissue pathology.

Details

Serval ID
serval:BIB_AC44163FA6B2
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
T cell affinity regulates asymmetric division, effector cell differentiation, and tissue pathology.
Journal
Immunity
Author(s)
King C.G., Koehli S., Hausmann B., Schmaler M., Zehn D., Palmer E.
ISSN
1097-4180 (Electronic)
ISSN-L
1074-7613
Publication state
Published
Issued date
2012
Peer-reviewed
Oui
Volume
37
Number
4
Pages
709-720
Language
english
Notes
Publication types: Journal Article ; Research Support, Non-U.S. Gov't
Abstract
The strength of interactions between T cell receptors and the peptide-major histocompatibility complex (pMHC) directly modulates T cell fitness, clonal expansion, and acquisition of effector properties. Here we show that asymmetric T cell division is an important mechanistic link between increased signal strength, effector differentiation, and the ability to induce tissue pathology. Recognition of pMHC above a threshold affinity drove responding T cells into asymmetric cell division. The ensuing proximal daughters underwent extensive division and differentiated into short-lived effector cells expressing the integrin VLA-4, allowing the activated T cell to infiltrate and mediate destruction of peripheral target tissues. In contrast, T cells activated by below-threshold antigens underwent symmetric division, leading to abortive clonal expansion and failure to fully differentiate into tissue-infiltrating effector cells. Antigen affinity and asymmetric division are important factors that regulate fate specification in CD8(+) T cells and predict the potential of a self-reactive T cell to mediate tissue pathology.
Keywords
Animals, Cell Differentiation, Cell Division, Cells, Cultured, Ligands, Lymphocyte Activation, Mice, Mice, Inbred C57BL, Phenotype, Receptors, Antigen, T-Cell/immunology, T-Lymphocytes/cytology, T-Lymphocytes/immunology
Pubmed
Web of science
Open Access
Yes
Create date
08/01/2013 17:43
Last modification date
20/08/2019 15:16
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