Publication Date:
2014-11-29
Description:
T cell responses are initiated by antigen and promoted by a range of costimulatory signals. Understanding how T cells integrate alternative signal combinations and make decisions affecting immune response strength or tolerance poses a considerable theoretical challenge. Here, we report that T cell receptor (TCR) and costimulatory signals imprint an early, cell-intrinsic, division fate, whereby cells effectively count through generations before returning automatically to a quiescent state. This autonomous program can be extended by cytokines. Signals from the TCR, costimulatory receptors, and cytokines add together using a linear division calculus, allowing the strength of a T cell response to be predicted from the sum of the underlying signal components. These data resolve a long-standing costimulation paradox and provide a quantitative paradigm for therapeutically manipulating immune response strength.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Marchingo, Julia M -- Kan, Andrey -- Sutherland, Robyn M -- Duffy, Ken R -- Wellard, Cameron J -- Belz, Gabrielle T -- Lew, Andrew M -- Dowling, Mark R -- Heinzel, Susanne -- Hodgkin, Philip D -- New York, N.Y. -- Science. 2014 Nov 28;346(6213):1123-7. doi: 10.1126/science.1260044.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia. Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia. ; Hamilton Institute, National University of Ireland, Maynooth, Ireland. ; Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia. Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia. The Royal Melbourne Hospital, Parkville, VIC, Australia. ; Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, Parkville, VIC, Australia. Department of Medical Biology, The University of Melbourne, Parkville, VIC, Australia. hodgkin@wehi.edu.au.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/25430770" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Antigens/*immunology
;
CD8-Positive T-Lymphocytes/cytology/*immunology
;
Cell Division
;
Cell Proliferation
;
Cytokines/*immunology
;
*Immune Tolerance
;
Lymphocyte Activation
;
Mice
;
Receptors, Antigen, T-Cell/*immunology
;
Signal Transduction
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
