PMID- 24391638
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140106
LR  - 20220129
IS  - 1664-3224 (Print)
IS  - 1664-3224 (Electronic)
IS  - 1664-3224 (Linking)
VI  - 4
DP  - 2013
TI  - Mathematical Model of Naive T Cell Division and Survival IL-7 Thresholds.
PG  - 434
LID - 10.3389/fimmu.2013.00434 [doi]
LID - 434
AB  - We develop a mathematical model of the peripheral naive T cell population to 
      study the change in human naive T cell numbers from birth to adulthood, 
      incorporating thymic output and the availability of interleukin-7 (IL-7). The 
      model is formulated as three ordinary differential equations: two describe T cell 
      numbers, in a resting state and progressing through the cell cycle. The third is 
      introduced to describe changes in IL-7 availability. Thymic output is a 
      decreasing function of time, representative of the thymic atrophy observed in 
      aging humans. Each T cell is assumed to possess two interleukin-7 receptor 
      (IL-7R) signaling thresholds: a survival threshold and a second, higher, 
      proliferation threshold. If the IL-7R signaling strength is below its survival 
      threshold, a cell may undergo apoptosis. When the signaling strength is above the 
      survival threshold, but below the proliferation threshold, the cell survives but 
      does not divide. Signaling strength above the proliferation threshold enables 
      entry into cell cycle. Assuming that individual cell thresholds are log-normally 
      distributed, we derive population-average rates for apoptosis and entry into cell 
      cycle. We have analyzed the adiabatic change in homeostasis as thymic output 
      decreases. With a parameter set representative of a healthy individual, the model 
      predicts a unique equilibrium number of T cells. In a parameter range 
      representative of persistent viral or bacterial infection, where naive T cell 
      cycle progression is impaired, a decrease in thymic output may result in the 
      collapse of the naive T cell repertoire.
FAU - Reynolds, Joseph
AU  - Reynolds J
AD  - Department of Applied Mathematics, School of Mathematics, University of Leeds , 
      Leeds , UK.
FAU - Coles, Mark
AU  - Coles M
AD  - Centre for Immunology and Infection, University of York , York , UK.
FAU - Lythe, Grant
AU  - Lythe G
AD  - Department of Applied Mathematics, School of Mathematics, University of Leeds , 
      Leeds , UK.
FAU - Molina-Paris, Carmen
AU  - Molina-Paris C
AD  - Department of Applied Mathematics, School of Mathematics, University of Leeds , 
      Leeds , UK.
LA  - eng
GR  - BB/G023395/1/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - G0601156/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
DEP - 20131223
PL  - Switzerland
TA  - Front Immunol
JT  - Frontiers in immunology
JID - 101560960
PMC - PMC3870322
OTO - NOTNLM
OT  - IL-7, T cell
OT  - IL-7R
OT  - homeostasis
OT  - mathematical model
OT  - threshold
OT  - thymic output
EDAT- 2014/01/07 06:00
MHDA- 2014/01/07 06:01
PMCR- 2013/01/01
CRDT- 2014/01/07 06:00
PHST- 2013/07/31 00:00 [received]
PHST- 2013/11/22 00:00 [accepted]
PHST- 2014/01/07 06:00 [entrez]
PHST- 2014/01/07 06:00 [pubmed]
PHST- 2014/01/07 06:01 [medline]
PHST- 2013/01/01 00:00 [pmc-release]
AID - 10.3389/fimmu.2013.00434 [doi]
PST - epublish
SO  - Front Immunol. 2013 Dec 23;4:434. doi: 10.3389/fimmu.2013.00434. eCollection 
      2013.