The influencing factors on T cell differentiation and the role of regulatory T cells in allergic immune responses : The influencing factors on T cell differentiation and the role of regulatory T cells in allergic immune responses
- 발행기관 고려대학교
- 발행년도 2007
- 학위수여년월 2007. 2
- 학위명 박사
- 학과 대학원 의학과 내과학전공
- 식별자(기타) DL:000018552391
- 서지제어번호 000045344430
초록/요약
Background : Antigen-presenting dendritic cells (DCs) are the principal cells that orchestrate adaptive immunity, while CD4+CD25+ T regulatory cells (Tregs) are known to regulate the immunologic balance. Many reports have shown that T helper 2 (Th2) responses to allergens are usually suppressed by Tregs. We purposed to clarify the role of DCs and CD4+CD25+ Tregs in the development of Th2 responses and investigated the conditions that contribute to the differentiation of CD4+ T cells. Methods : Male BALB/c mice were divided into OVA-challenged and control groups, and DCs, CD4+CD25- T cells, and Tregs were purified from their thymuses and spleens. OVA-sensitized DCs were obtained by the same method. Purified DCs and CD4+CD25- T cells were then cocultured with or without Tregs under various conditions [e.g., with or without OVA323-339, granulocyte-macrophage-stimulating factor (GM-CSF), interferon- γ (IFN-γ), and interleukine-10 (IL-10)]. The level of IL-4 was analyzed after coculture. Results : The level of IL-4 was significantly higher in cells cocultured with GM-CSF and in cells cocultured with Tregs. Moreover, OVA-sensitized DCs cocultured with 1 or 5 μg/ml of OVA had significantly increased IL-4 levels. For niave DCs, only a high dose of OVA increased IL-4 production. When the cells were cultured with IL-10, the level of IL-4 decreased significantly. Furthermore, CD4+CD25- T cells cocultured with IL-10 exhibited a greater decrease in IL-4 level than those cultured without Tregs. The proportion of CD4+CD25+ Tregs increased slightly when cultured with IL-10. Conclusions : GM-CSF and allergen exposure are important for the development of Th2 immune responses. Low-level allergen exposure activates pre-sensitized DCs, but a high allergen dose is necessary to activate naïve DCs. In addition, IL-10 induces CD4+CD25- T cells to develop into CD4+CD25+ Tregs. Natural Tregs enhance the development of Th2 responses, while induced-Tregs suppress it, indicating that different Tregs have different fuctions.
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目 次
Abstract
1. Introduction
2. Materials and methods
3. Results
4. Discussion
5. References
6. Figure legends
7. Figures
