Modeling IL-2 gene expression in human regulatory T cells.
Interleukin-2 (IL-2) is one of the first cytokines to be expressed by T helper cells (Th cells) after antigen-specific stimulation. In contrast, regulatory T cells (T(reg) cells) do not express IL-2, although they are activated via the same pathways. In regulatory T cells the additional transcription factor FoxP3 is expressed. Using intracellular measurement of the transcription factors NFAT and FoxP3 as well as the cytokine IL-2 on single cell level we revealed a small fraction of IL-2 expressing T(reg) cells. Furthermore, these data enabled us to develop initial mathematical models describing gene expression of IL-2 in individual cells. The models are adapted to data from human regulatory T cells. Based on statistical tests of available flow cytometric data it seems reasonable that not only the amount of the transcription factors NFAT and FoxP3 is important but also their concentration ratio. We discuss specific problems of modeling gene expression on single cell level taking IL-2 expression as an example.
Benary
Manuela
M
Institute for Theoretical Biology, Humboldt University of Berlin, Invalidenstr. 43, 10115 Berlin, Germany. manuela.benary@cms.hu-berlin.de
Bendfeldt
Hanna
H
Baumgrass
Ria
R
Herzel
Hanspeter
H
D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics* / Q000378:metabolism; D008957:Models, Genetic; D008962:Models, Theoretical; D011401:Promoter Regions, Genetic; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000502:physiology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology*; D014158:Transcription, Genetic
C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D007376:Interleukin-2