Th1 and Th2 cells, which produce distinct sets of cytokines, differentially express several chemokine receptors that may regulate their tissue-specific localization. Although the expression pattern and regulation of chemokines are likely to play a critical role in many immunopathological processes, they remain largely unknown. Here, we investigated the requirements for Th1 and Th2 cells to produce the Th2 cell-attracting chemokines thymus and activation-regulated chemokine (TARC), macrophage-derived chemokine (MDC) and I-309. TCR triggering of Th1 and Th2 cells leads to production of MDC and I-309 (CCR4 and CCR8 ligands, respectively), whereas TARC (CCR4 ligand) is selectively produced by Th2 cells. Secretion of these chemokines appears to be independent of endogenous production of IL-4 and IFN-gamma. IL-12 and IFN-alpha, cytokines that promote the differentiation of human Th1 cells, selectively inhibit secretion and mRNA expression of MDC and I-309 by Th1 cells. Suppression of I-309 secretion results in a decreased chemotactic effect on L1.2 cells transfected with human CCR8, indicating that IL-12 and IFN-alpha may inhibit the recruitment of CCR8-expressing cells such as Th2 cells. The inhibition of Th2 cell-attracting chemokines MDC and I-309 illustrates a novel mechanism by which IL-12 and IFN-alpha could promote and maintain an ongoing Th1 response.

JOURNAL ARTICLE Animal B-Lymphocytes/DRUG EFFECTS/IMMUNOLOGY/METABOLISM Cell Differentiation/DRUG EFFECTS Cell Line Cells, Cultured Chemokines, CC/ANTAGONISTS & INHIB/*BIOSYNTHESIS/GENETICS/ METABOLISM Chemotaxis, Leukocyte/DRUG EFFECTS/IMMUNOLOGY Cytokines/ANTAGONISTS & INHIB/*BIOSYNTHESIS/GENETICS/METABOLISM Dose-Response Relationship, Drug Human Interferon Type II/ANALYSIS/PHYSIOLOGY Interferon-alpha/METABOLISM/*PHARMACOLOGY Interleukin-12/METABOLISM/*PHARMACOLOGY Interleukin-4/ANALYSIS/PHYSIOLOGY Ligands Lymphocyte Transformation Mice Receptors, Antigen, T-Cell/*IMMUNOLOGY Receptors, Chemokine/GENETICS/IMMUNOLOGY/METABOLISM RNA, Messenger/GENETICS/METABOLISM Th1 Cells/CYTOLOGY/DRUG EFFECTS/IMMUNOLOGY/*METABOLISM Th2 Cells/DRUG EFFECTS/IMMUNOLOGY/METABOLISM Transfection

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