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Bulletin of Mathematical Biology : Volume 61, Issue 2, March 1999

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Bulletin of Mathematical Biology : Volume 60

Bulletin of Mathematical Biology : Volume 59

Th1/Th2 differentiation and cross-regulation

Content Provider	Springer Nature Link
Author	Fishman, Michael A. Perelson, Alan S.
Copyright Year	1999
Abstract	The T helper (Th) phenotypes, Th1/Th2, are acquired upon interaction of a naive T helper cell and an antigen presenting cell (APC). Naive T helper cells may differentiate into either phenotype, and the actual outcome is determined by the density and avidity of the antigenic determinants presented by the APC, and the APCs inherent costimulatory properties. Until recently it was thought that differentiation is further affected by cytokines. However, Murphy et al. (1996, J. Exp. Med. 183, 901) have demonstrated that the experimental results, formerly interpreted as Th1/Th2 differentiation, in effect comprise an observation of two consecutive processes. (i) An interaction between naive T cells and APC creates a mixture of mature cells irreversibly committed to Th1 or Th2 phenotype. (ii) Subsequent addition of regulatory cytokines, promotes expansion of one phenotype while suppressing the other. The consequent shift in the per culture production of marker cytokines mimics the appearance of a cellular phenotype switch. We present and analyse a mathematical model that extrapolates these experimental facts into systemic behavior during an immune response. Despite the fact that differentiation produces cells of Th1 and Th2 phenotypes with the same receptor specificity, our results indicate that competition for antigenic stimulation, mediated by the APCs, combines with cytokine mediated cross-suppression between phenotypes to yield a response that is eventually dominated by T helper cells that are uniform in both receptor specificity (clonotype) and in cytokine secretion phenotype.
Starting Page	403
Ending Page	436
Page Count	34
File Format	PDF
ISSN	00928240
Journal	Bulletin of Mathematical Biology
Volume Number	61
Issue Number	3
e-ISSN	15229602
Language	English
Publisher	Springer-Verlag
Publisher Date	1999-01-01
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Mathematical Biology in General
Content Type	Text
Resource Type	Article
Subject	Neuroscience Biochemistry, Genetics and Molecular Biology Mathematics Pharmacology Immunology Computational Theory and Mathematics Environmental Science Agricultural and Biological Sciences

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