Regulation of the Interleukin (IL)-12R β2 Subunit Expression in Developing T Helper 1 (Th1) and Th2 Cells

DOI PDF 被引用文献31件
  • Susanne J. Szabo
    From the *Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110; and the ‡Department of Inflammation/Autoimmune Diseases Hoffmann La-Roche Inc., Nutley, New Jersey 07110
  • Anand S. Dighe
    From the *Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110; and the ‡Department of Inflammation/Autoimmune Diseases Hoffmann La-Roche Inc., Nutley, New Jersey 07110
  • Ueli Gubler
    From the *Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110; and the ‡Department of Inflammation/Autoimmune Diseases Hoffmann La-Roche Inc., Nutley, New Jersey 07110
  • Kenneth M. Murphy
    From the *Department of Pathology, Washington University School of Medicine, St. Louis, Missouri 63110; and the ‡Department of Inflammation/Autoimmune Diseases Hoffmann La-Roche Inc., Nutley, New Jersey 07110

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<jats:p>The developmental commitment to a T helper 1 (Th1)- or Th2-type response can significantly influence host immunity to pathogens. Extinction of the IL-12 signaling pathway during early Th2 development provides a mechanism that allows stable phenotype commitment. In this report we demonstrate that extinction of IL-12 signaling in early Th2 cells results from a selective loss of IL-12 receptor (IL-12R) β2 subunit expression. To determine the basis for this selective loss, we examined IL-12R β2 subunit expression during Th cell development in response to T cell treatment with different cytokines. IL-12R β2 is not expressed by naive resting CD4+ T cells, but is induced upon antigen activation through the T cell receptor. Importantly, IL-4 and IFN-γ were found to significantly modify IL-12 receptor β2 expression after T cell activation. IL-4 inhibited IL-12R β2 expression leading to the loss of IL-12 signaling, providing an important point of regulation to promote commitment to the Th2 pathway. IFN-γ treatment of early developing Th2 cells maintained IL-12R β2 expression and restored the ability of these cells to functionally respond to IL-12, but did not directly inhibit IL-4 or induce IFN-γ production. Thus, IFN-γ may prevent early Th cells from premature commitment to the Th2 pathway. Controlling the expression of the IL-12R β2 subunit could be an important therapeutic target for the redirection of ongoing Th cell responses.</jats:p>

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