Autocrine Regulation of IL-12 Receptor Expression Is Independent of Secondary IFN-γ Secretion and not Restricted to T and NK Cells
العنوان: | Autocrine Regulation of IL-12 Receptor Expression Is Independent of Secondary IFN-γ Secretion and not Restricted to T and NK Cells |
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المؤلفون: | Deborah K. Thibodeaux, Sharon E. Hunter, Kristine E. Waldburger, Judy L. Bliss, William L. Trepicchio, Joseph P. Sypek, Kyriaki Dunussi-Joannopoulos, Samuel J. Goldman, John P. Leonard |
المصدر: | The Journal of Immunology. 163:5257-5264 |
بيانات النشر: | The American Association of Immunologists, 1999. |
سنة النشر: | 1999 |
مصطلحات موضوعية: | Immunology, Immunology and Allergy |
الوصف: | The biological response to IL-12 is mediated through specific binding to a high affinity receptor complex composed of at least two subunits (designated IL-12Rβ1 and IL-12Rβ2) that are expressed on NK cells and activated T cells. The selective loss of IL-12Rβ2 expression during Th2 T cell differentiation suggests that regulation of this receptor component may govern IL-12 responsiveness. In murine assays, down-regulation of IL-12Rβ2 expression can be prevented by treatment with IFN-γ, indicating that receptor expression and hence IL-12 responsiveness may be regulated, at least in part, by the local cytokine milieu. In this study, we report that cellular expression of both IL-12Rβ1 and β2 mRNA is increased in the lymph nodes of naive mice following systemic administration of murine rIL-12 (rmIL-12). Changes in IL-12R mRNA were associated with increased IFN-γ secretion following ex vivo activation of lymph node cells with rmIL-12, indicating the presence of a functional receptor complex. Expression of IL-12R mRNA was not restricted to lymph node T cells, and its autocrine regulation was independent of secondary IFN-γ secretion. Data from fractionated lymph node cells as well as rmIL-12-treated B cell-deficient mice suggest that IL-12-responsive B cells may represent an alternative cellular source for IFN-γ production. However, the strength of the biological response to rmIL-12 is not governed solely by receptor expression, as rmIL-12-induced IFN-γ secretion from cultured lymph node cells is accessory cell dependent and can be partially blocked by inhibition of B7 costimulation. |
تدمد: | 1550-6606 0022-1767 |
DOI: | 10.4049/jimmunol.163.10.5257 |
URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_________::54c6b597cbaccce9c8b0a3fcfa1f41da https://doi.org/10.4049/jimmunol.163.10.5257 |
رقم الانضمام: | edsair.doi...........54c6b597cbaccce9c8b0a3fcfa1f41da |
قاعدة البيانات: | OpenAIRE |
تدمد: | 15506606 00221767 |
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DOI: | 10.4049/jimmunol.163.10.5257 |