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PMID: 17360353 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

A model of immune regulation as a consequence of randomized lymphocyte division and death times.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 104 ·No. 12 ·2007-03-20 ·Pages 5032-7

Hawkins ED, Turner ML, Dowling MR, van Gend C, Hodgkin PD

Abstract

The magnitude of an adaptive immune response is controlled by the interplay of lymphocyte quiescence, proliferation, and apoptosis. How lymphocytes integrate receptor-mediated signals influencing these cell fates is a fundamental question for understanding this complex system. We examined how lymphocytes interleave times to divide and die to develop a mathematical model of lymphocyte growth regulation. This model provides a powerful method for fitting and analyzing fluorescent division tracking data and reveals how summing receptor-mediated kinetic changes can modify the immune response progressively from rapid tolerance induction to strong immunity. An important consequence of our results is that intrinsic variability in otherwise identical cells, usually dismissed as noise, may have evolved to be an essential feature of immune regulation.

MeSH Terms
Animals Cell Death Cell Division Cell Survival Immunity, Cellular/immunology Lymphocytes/cytology Male Mice Mice, Inbred C57BL Models, Biological Time Factors
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Hawkins E D
Immunology Division, The Walter and Eliza Hall Institute of Medical Research, 1G Royal Parade, Parkville, Victoria 3050, Australia.
Turner M L
Dowling M R
van Gend C
Hodgkin P D
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.0700026104
Published
2007-03-20
Epub
2007-00-14
Pages
5032-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC1821128
Subset
IM
External Links
PubMed source DOI: 10.1073/pnas.0700026104 PMC Full Text View journal details
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