IL-2 regulates expansion of CD4+ T cell populations by affecting cell death: insights from modeling CFSE data.
It is generally accepted that IL-2 influences the dynamics of populations of T cells in vitro and in vivo. However, which parameters for cell division and/or death are affected by IL-2 is not well understood. To get better insights into the potential ways of how IL-2 may influence the population dynamics of T cells, we analyze data on the dynamics of CFSE-labeled polyclonal CD4(+) T lymphocytes in vitro after anti-CD3 stimulation at different concentrations of exogenous IL-2. Inferring cell division and death rates from CFSE-delabeling experiments is not straightforward and requires the use of mathematical models. We find that to adequately describe the dynamics of T cells at low concentrations of exogenous IL-2, the death rate of divided cells has to increase with the number of divisions cells have undergone. IL-2 hardly affects the average interdivision time. At low IL-2 concentrations 1) fewer cells are recruited into the response and successfully complete their first division; 2) the stochasticity of cell division is increased; and 3) the rate, at which the death rate increases with the division number, increases. Summarizing, our mathematical reinterpretation suggests that the main effect of IL-2 on the in vitro dynamics of naive CD4(+) T cells occurs by affecting the rate of cell death and not by changing the rate of cell division.
Ganusov
Vitaly V
VV
Theoretical Biology, Utrecht University, Utrecht, The Netherlands. v.v.ganusov@uu.nl
Milutinović
Dejan
D
De Boer
Rob J
RJ
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D016923:Cell Death / Q000276:immunology*; D049109:Cell Proliferation; D005452:Fluoresceins; D007376:Interleukin-2 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008962:Models, Theoretical; D013388:Succinimides
C087165:5-(6)-carboxyfluorescein diacetate succinimidyl ester; D005452:Fluoresceins; D007376:Interleukin-2; D013388:Succinimides