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Development of Th1-inducing capacity in myeloid dendritic cells requires environmental instruction.




 

J Immunol. 2000 May 1;164(9):4507-12. Unique Identifier : AIDSLINE

Dendritic cells (DC) are key initiators of primary immune responses. Myeloid DC can secrete IL-12, a potent Th1-driving factor, and are often viewed as Th1-promoting APC. Here we show that neither a Th1- nor a Th2-inducing function is an intrinsic attribute of human myeloid DC, but both depend on environmental instruction. Uncommitted immature DC require exposure to IFN-gamma, at the moment of induction of their maturation or shortly thereafter, to develop the capacity to produce high levels of IL-12p70 upon subsequent contact with naive Th cells. This effect is specific for IFN-gamma and is not shared by other IL-12-inducing factors. Type 1-polarized effector DC, matured in the presence of IFN-gamma, induce Th1 responses, in contrast to type 2-polarized DC matured in the presence of PGE2 that induce Th2 responses. Type 1-polarized effector DC are resistant to further modulation, which may facilitate their potential use in immunotherapy.

JOURNAL ARTICLE Cell Communication/*IMMUNOLOGY Cell Differentiation/IMMUNOLOGY Cells, Cultured Coculture Dendritic Cells/CYTOLOGY/*IMMUNOLOGY/*METABOLISM Dinoprostone/PHYSIOLOGY Human Interferon Type II/BIOSYNTHESIS/PHYSIOLOGY Interleukin-12/BIOSYNTHESIS Lymphocyte Transformation Monocytes/CYTOLOGY/*IMMUNOLOGY/METABOLISM Support, Non-U.S. Gov't Th1 Cells/*CYTOLOGY/*IMMUNOLOGY/METABOLISM Th2 Cells/CYTOLOGY/IMMUNOLOGY/METABOLISM



 




Information in this article was accurate in July 30, 2000. The state of the art may have changed since the publication date. This material is designed to support, not replace, the relationship that exists between you and your doctor. Always discuss treatment options with a doctor who specializes in treating HIV.