TLR2 Agonists Enhance CD8+Foxp3+ Regulatory T Cells and Suppress Th2 Immune Responses during Allergen Immunotherapy
| Autor: | Ching-Yuang Lin, Dau-Ming Niu, Kuender D. Yang, Yi-Giien Tsai, Jien-Wen Chien |
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| Rok vydání: | 2010 |
| Předmět: |
Male
Adolescent T cell Blotting Western Immunology Population Enzyme-Linked Immunosorbent Assay chemical and pharmacologic phenomena Cell Separation CD8-Positive T-Lymphocytes T-Lymphocytes Regulatory Lipopeptides Th2 Cells Adjuvants Immunologic Antigen T-Lymphocyte Subsets Hypersensitivity medicine Animals Humans Immunology and Allergy Antigens Dermatophagoides IL-2 receptor Child education Interleukin 4 education.field_of_study biology Pyroglyphidae FOXP3 Forkhead Transcription Factors hemic and immune systems Flow Cytometry Toll-Like Receptor 2 Interleukin 10 medicine.anatomical_structure Granzyme Desensitization Immunologic Child Preschool biology.protein Female |
| Zdroj: | The Journal of Immunology. 184:7229-7237 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | Pam3CSK4, a synthetic TLR2 ligand, has been shown to expand CD4+ regulatory T cells (Treg cells). Less is known about the function of CD8+ Treg cells than about the function of CD4+ Treg cells generated during allergen-specific immunotherapy (IT). This study investigated whether Dermatophagoides pteronyssinus-specific IT could expand the CD8+CD25+Foxp3+ Treg population and whether Pam3CSK4 could enhance the Treg population. PBMCs were isolated from healthy control subjects and from mite-sensitive asthmatic patients during IT at three specific times: before IT and 6 mo and 1 y after the maximum-tolerated dose. This study was performed without a placebo-controlled group. D. pteronyssinus-specific IT induced a significant increase in CD8+Foxp3+ Treg cells expressing intracellular IL-10 and granzyme B. Costimulation of PBMCs with Pam3CSK4 and D. pteronyssinus 2 expanded the CD8+CD25+Foxp3+ Treg population and inhibited D. pteronyssinus 2-induced IL-4 production. Pam3CSK4-treated CD8+CD25+ Treg cells directly suppressed CD4+ T cell proliferation by cell-contact inhibition. TUNEL revealed that CD8+CD25+ Treg cells, but not CD4+CD25+ Treg cells, directly induced CD4+CD45ROhi+ apoptosis. Our results provide direct evidence that Pam3CSK4 induces an immunomodulatory effect by inducing CD8+ Treg cells; therefore, it may be a good adjuvant for the treatment of mite allergies. |
| Databáze: | OpenAIRE |
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