Regulation of IL-4 expression by activation of individual alleles.
To study the in vivo role of IL-4-expressing cells, we developed a strategy to tag these cells, by generating mice in which one IL-4 allele was replaced with a cDNA encoding the human CD2 (huCD2) cell-surface molecule. Expression of the huCD2 reporter was, like IL-4, restricted to the appropriately polarized T helper 2 cells. However, most of the cells expressed only the IL-4 or the targeted allele. Analysis of the frequency of monoallelic versus biallelic expression suggests that the activation of each individual allele is regulated by a stochastic process whose probability can be augmented by increasing the strength of signal delivered through the TCR. Allele-specific activation may be a general feature of cytokine regulation that contributes to the functional diversity within T helper cell subpopulations.
Rivière
I
I
Molecular Pathogenesis Program, Skirball Institute of Biomolecular Medicine, New York University Medical Center, New York 10016, USA.
Sunshine
M J
MJ
Littman
D R
DR
D000483:Alleles; D000818:Animals; D018801:CD2 Antigens / Q000096:biosynthesis / Q000235:genetics; D018076:DNA, Complementary / Q000235:genetics; D005786:Gene Expression Regulation / Q000235:genetics*; D017930:Genes, Reporter / Q000235:genetics; D005822:Genetic Vectors / Q000235:genetics; D015847:Interleukin-4 / Q000096:biosynthesis / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011948:Receptors, Antigen, T-Cell / Q000502:physiology; D011995:Recombination, Genetic / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics; D013269:Stochastic Processes; D018418:Th2 Cells / Q000378:metabolism
D018801:CD2 Antigens; D018076:DNA, Complementary; D011948:Receptors, Antigen, T-Cell; D015847:Interleukin-4