Tissue-specific regulation of IL-4 mRNA expression in human tonsil

The cellular and molecular regulation of IL-4 mRNA expression in human tonsillar T lymphocytes was examined to define the mechanisms responsible for biphasic IL-4 mRNA expression in this lymphoid organ. Tonsillar T cells expressed IL-4 mRNA in a biphasic manner with peaks at 8 and 24 h after PHA stimulation. De novo protein synthesis was not required for IL-4 mRNA expression because cycloheximide treatment of tonsillar MNC did not ablate the response. Nuclear runoff assays demonstrated transcription of the IL-4 gene at 8 and 24 h, which was not affected by addition of actinomycin D. Separation of T cells into naive (CD45RAhi/CD29lo) and primed (CD45RAlo/CD29hi) subpopulations revealed that although naive and primed T cells expressed IL-4 mRNA at 8 h, the 24-h peak of IL-4 mRNA expression was solely due to primed (CD45RAlo/CD29hi) Th cells. This effect was tissue specific and IL specific in that 1) primed peripheral blood T cells had only one peak of IL-4 mRNA expression at 8 h and 2) in primed tonsillar T cells, mRNA expression of IL-2, IL-6 and IL-2 receptor and c-myc was not delayed. Thus, IL-4 mRNA expression in the tonsil differs depending on the surface expression of different isoforms of the leukocyte common Ag. The tissue- and stimulus-specific regulation of IL-4 mRNA in different lymphoid tissues may play an important role in regional immunoregulation.