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.
Secrist
H
H
Washington University School of Medicine, St. Louis, MO 63110.
Egan
M
M
Peters
M G
MG
D015703:Antigens, CD / Q000032:analysis; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D006801:Humans; D007156:Immunologic Memory; D066298:In Vitro Techniques; D019012:Integrin beta1; D015847:Interleukin-4 / Q000235:genetics*; D017493:Leukocyte Common Antigens / Q000032:analysis; D008213:Lymphocyte Activation; D014066:Palatine Tonsil / Q000276:immunology*; D012333:RNA, Messenger / Q000235:genetics; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*; D013997:Time Factors; D014158:Transcription, Genetic
D015703:Antigens, CD; D019012:Integrin beta1; D012333:RNA, Messenger; D015847:Interleukin-4; D017493:Leukocyte Common Antigens