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Inhibition by IL-12 and IFN-alpha of I-309 and macrophage-derived chemokine production upon TCR triggering of human Th1 cells.




 

Eur J Immunol. 2000 Apr;30(4):1030-9. Unique Identifier : AIDSLINE

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



 




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.