Expression of Thrombospondin in TGFβ-Treated APCs and Its Relevance to Their Immune Deviation-Promoting Properties
| Autor: | Bruce Turpie, Karl H. Hecker, J. Wayne Streilein, Sharmila Masli |
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| Rok vydání: | 2002 |
| Předmět: |
Transcription
Genetic Cellular differentiation Immunology Antigen-Presenting Cells Polymerase Chain Reaction Macrophage elastase Interferon-gamma Mice Transforming Growth Factor beta2 Immune system Antigens CD Transforming Growth Factor beta Histocompatibility Antigens Animals Immunology and Allergy RNA Messenger Antigen-presenting cell Thrombospondin Hybridomas CD40 biology Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Macrophages Models Immunological Transforming growth factor beta Interleukin-12 Cell biology Self Tolerance biology.protein Interleukin 12 Cytokines Thrombospondins |
| Zdroj: | The Journal of Immunology. 168:2264-2273 |
| ISSN: | 1550-6606 0022-1767 |
| Popis: | APCs deployed within iris/ciliary body are responsible for promoting anterior chamber-associated immune deviation following injection of Ag into the eye. TGFβ-2, a constituent of the ocular microenvironment, converts conventional APCs that are pulsed with Ag into cells that induce immune deviation when injected into naive mice. TGFβ-2-treated APCs under-express IL-12 and CD40, and over-express active TGFβ. We have examined transcriptional changes within macrophage hybridoma no. 59, which promotes Th1 cell differentiation, and TGFβ-2-treated no. 59 as well as macrophage hybridoma no. 63, both of which induce immune deviation similar to anterior chamber-associated immune deviation. Immune deviation-inducing hybridomas up-regulated expression of thrombospondin, TGFβ, IFN-α and β, murine macrophage elastase, and macrophage-inflammatory protein-2 genes, while down-regulating expression of the genes for NF-κB and CD40. Based on the known properties of these gene products, a model is proposed in which these gene products, alone and through interacting signaling pathways, confer upon conventional APCs the capacity to create and surround themselves with an immunomodulatory microenvironment. The model proposes that the pleiotropic effects of thrombospondin are primarily responsible for creating this microenvironment that is stabile, rich in active TGFβ and IFN-α and β, deficient in IL-12, and chemoattractant via macrophage-inflammatory protein-2 for NK T cells. It is further proposed that presentation of Ag to T cells in this microenvironment leads to their differentiation into regulatory cells that suppress Th1 cell-dependent immunogenic inflammation. |
| Databáze: | OpenAIRE |
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