Repository logo
  • English
  • 中文
Log In
Have you forgotten your password?
  1. Home
  2. College of Medicine / 醫學院
  3. Immunology / 免疫學研究所
  4. Study on the molecular mechanisms of induction and suppressive activity of Treg-of-B cells
 
  • Details

Study on the molecular mechanisms of induction and suppressive activity of Treg-of-B cells

Date Issued
2015
Date
2015
Author(s)
Lau, Ka-Yi
URI
http://ntur.lib.ntu.edu.tw//handle/246246/273098
Abstract
B cells are capable to induce immunologic tolerance despite their primary role in humoral immunity. Accumulating evidence with a particular focus on defining conventional B-2 cells can serve as antigen presenting cells to convert naïve CD4+CD25- T cells into regulatory T cells (so-called Treg-of-B cells) in vitro. The B cells primed regulatory T were found to exert a suppressive function on T-cell proliferation. Previous study has already revealed that the mechanism involved in the generation of Treg-of-B cells was in a contact-dependent manner. There was a reversal of suppressive function of Tregs when B cells cultured with T cells were separated by a trans-well membrane. According to the two-signal model of T-cell activation, activation of naïve antigen-specific CD4+ T cells is thought to require at least both stimulation of the T cell receptor (TCR) (Signal 1), and stimulation of costimulatory molecules (Signal 2). The cytokine signal (Signal 3) is additional signal which plays critical role for generating a robust and specialized T-cell response. Many cytokine signaling is transmitted via Janus kinase (JAK) - signal transducer and activator of transcription (STAT) pathway. In this study, we aim to (1) investigate whether costimulatory blockade by single blocking antibody could boost or dampen Treg-of-B-cell activation and (2) identify the phosphorylated STAT proteins which are involved in induction and suppressive function of Treg-of-B cells. To induce regulatory T cells stimulated by B-2 cells, naïve B cells were isolated from splenoctyes of BALB/c mice and then pulsed with OVA-peptide for a day. After that, OVA peptide-loaded B cells were co-cultured with naïve CD4+ T cells isolated from splenocytes of DO11.10 mice for 3 days without addition of exogenous cytokines. After a 3 day co-culture, CD4+ T cells were purified after depletion of B220+ cells. The suppressive function of isolated CD4+ T cells was further examined. The effect of costimulatory blockade on B cells generated regulatory T cell was examined by using single neutralizing blocking antibody. On the other hand, to study the involvement of phosphorylated STAT proteins during induction and suppressive function of Treg-of-B cells, naïve B cells were co-cultured with naïve CD4+ T cells which both isolated from splenocytes of BALB/c mice under the stimulation of anti-CD3/CD28 for 3 days. The cell lysates of CD4+ T cells and re-stimulated CD4+ T cells were harvested after depletion of B220+ cells during induction and suppressive function at various time points respectively. We found that OVA-peptide loaded B-2 cells can serve as antigen presenting cells to induce CD4+ T cells into regulatory T cells (Treg-of-B cells). We further demonstrated that B-2 cells expressed GITRL, ICAM-1, ICOSL, CD70 and OX40L as antigen presenting cells to CD4+ T cells. However, there was no reversal or enhancement of suppressive function of Treg-of-B cells on T-cell proliferation under the treatment of particular single blocking antibody during induction. Only under anti-GITR, the expression of GITR on Treg-of-B cells was significantly down-regulated. On the other hand, we identified that the phosphorylated Stat1, Stat3, Stat5 and Stat6 were involved in the induction and suppressive function of Treg-of-B cells. Our results confirmed that conventional B-2 cells can modulate immune responses through priming T cells into regulatory T cells. Also, we demonstrated that B cells generated regulatory T cells was not through single costimulatory pathways. We further demonstrated that the expression of GITR on Treg-of-B cells was not a critical molecule to exert suppressive function on T-cell proliferation. On the other hand, we have shown that phosphorylated Stat1, Stat3, Stat5 and Stat6 were involved in the induction and suppressive activity of Treg-of-B cells which is different from nTregs and other inducible Tregs. These findings might help us on identifying Treg-of-B cells into distinct subsets of Treg cells.
Subjects
B-2 cells
regulatory T cells
co-stimulatory molecules
pStats
immune regulation
Type
thesis

臺大位居世界頂尖大學之列,為永久珍藏及向國際展現本校豐碩的研究成果及學術能量,圖書館整合機構典藏(NTUR)與學術庫(AH)不同功能平台,成為臺大學術典藏NTU scholars。期能整合研究能量、促進交流合作、保存學術產出、推廣研究成果。

To permanently archive and promote researcher profiles and scholarly works, Library integrates the services of “NTU Repository” with “Academic Hub” to form NTU Scholars.

總館學科館員 (Main Library)
醫學圖書館學科館員 (Medical Library)
社會科學院辜振甫紀念圖書館學科館員 (Social Sciences Library)

開放取用是從使用者角度提升資訊取用性的社會運動,應用在學術研究上是透過將研究著作公開供使用者自由取閱,以促進學術傳播及因應期刊訂購費用逐年攀升。同時可加速研究發展、提升研究影響力,NTU Scholars即為本校的開放取用典藏(OA Archive)平台。(點選深入了解OA)

  • 請確認所上傳的全文是原創的內容,若該文件包含部分內容的版權非匯入者所有,或由第三方贊助與合作完成,請確認該版權所有者及第三方同意提供此授權。
    Please represent that the submission is your original work, and that you have the right to grant the rights to upload.
  • 若欲上傳已出版的全文電子檔,可使用Open policy finder網站查詢,以確認出版單位之版權政策。
    Please use Open policy finder to find a summary of permissions that are normally given as part of each publisher's copyright transfer agreement.
  • 網站簡介 (Quickstart Guide)
  • 使用手冊 (Instruction Manual)
  • 線上預約服務 (Booking Service)
  • 方案一:臺灣大學計算機中心帳號登入
    (With C&INC Email Account)
  • 方案二:ORCID帳號登入 (With ORCID)
  • 方案一:定期更新ORCID者,以ID匯入 (Search for identifier (ORCID))
  • 方案二:自行建檔 (Default mode Submission)
  • 方案三:學科館員協助匯入 (Email worklist to subject librarians)

Built with DSpace-CRIS software - Extension maintained and optimized by 4Science