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Retinoic acids exert direct effects on T cells to suppress Th1 development and enhance Th2 development via retinoic acid receptors
- Source :
- International Immunology. 15:1017-1025
- Publication Year :
- 2003
- Publisher :
- Oxford University Press (OUP), 2003.
-
Abstract
- The vitamin A metabolite, retinoic acid (RA), affects Th1 and Th2 development. The effect is partly exerted through the modulation of antigen-presenting cell functions, but it remains unclear whether RA directly exerts its effect on T cells to influence Th1/Th2 development. To clarify this problem, we used two experimental systems with isolated T cells in vitro. In one system, isolated CD4+CD8+ thymocytes differentiated into Th1 and Th2 by two transient stimulations with defined combinations of ionomycin and phorbol myristate acetate followed by treatment with IL-2 and IL-4 and/or IL-12. In the second system, functional differentiation was induced in purified naive CD4 T cells from DO-11.10 TCR-transgenic and RAG-2-deficient mice with cytokines and antibodies to CD3 and CD28. In both systems, all-trans-RA ator = 1 nM concentrations suppressed Th1 development, but enhanced Th2 development. 9-cis-RA elicited similar effects. The optimal enhancement of Th2 development in the second system, however, was achieved with a delayed addition of RA. The presence of RA during the initial stimulation period often suppressed Th2 development. The RA receptor (RAR) antagonists, LE540 and LE135, but not the retinoic X receptor (RXR) antagonist, PA452, inhibited the effect of RA on Th1/Th2 development. Accordingly, the RAR agonists, Am80 and Tp80, but not the RXR agonists, HX600 and TZ335, mimicked the effect of RA. The RXR agonists enhanced the effect of the RAR agonists only slightly, if at all. These results indicate that, via RAR, RA directly suppresses Th1 development and directly enhances Th2 development with its timely addition.
- Subjects :
- Male
Time Factors
CD3 Complex
Receptors, Retinoic Acid
T-Lymphocytes
Retinoic acid
Lymphocyte Activation
Mice
chemistry.chemical_compound
Histocompatibility Antigens
Immunology and Allergy
Vitamin A
Receptor
Alitretinoin
Mice, Knockout
Reverse Transcriptase Polymerase Chain Reaction
Receptors, Interleukin-12
CD28
Cell Differentiation
General Medicine
Flow Cytometry
Interleukin-12
Interleukin-10
Cell biology
DNA-Binding Proteins
Biochemistry
Proto-Oncogene Proteins c-maf
Ionomycin
Immunology
Mice, Transgenic
Tretinoin
GATA3 Transcription Factor
Biology
Retinoid X receptor
Antibodies
Interferon-gamma
Th2 Cells
CD28 Antigens
Proto-Oncogene Proteins
Animals
Dose-Response Relationship, Drug
Receptors, Interleukin
Th1 Cells
Receptors, Interleukin-4
Retinoic acid receptor
Retinoid X Receptors
Gene Expression Regulation
Nuclear receptor
chemistry
Trans-Activators
Interleukin-2
Interleukin-4
Interleukin-5
T-Box Domain Proteins
CD8
Transcription Factors
Subjects
Details
- ISSN :
- 14602377
- Volume :
- 15
- Database :
- OpenAIRE
- Journal :
- International Immunology
- Accession number :
- edsair.doi.dedup.....bf59a155a75251ee226e92095e92399b