2014 Fiscal Year Annual Research Report
Mechanisms of regulatory T-cell control of humoral immunity
| Project/Area Number |
25860356
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| Research Institution | Osaka University |
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Principal Investigator |
ウィング ジェイムス 大阪大学, 免疫学フロンティア研究センター, 特任助教(常勤) (00648694)
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| Project Period (FY) |
2013-04-01 – 2015-03-31
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| Keywords | Regulatory T-cells / T Follicular helper / Vaccination / Antibody responses |
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| Outline of Annual Research Achievements |
Regulatory T-cells (Tregs) have a critical role in the control of humoral immunity, which is relevant to both autoimmunity and vaccination. This project set out to determine the mechanism by which regulatory T-cells and their follicular resident counterparts Follicular regulatory T-cells (Tfr) are able to exert this function.
This goal has been met, I discovered that Tregs and Tfr control the formation of T-follicular helper cells, which are critical for the delivery of help to antigen producing B-cells, via the inhibitory receptor CTLA-4. CTLA-4 allows Tregs and Tfr to control the co-stimulatory ability of antigen presenting cells by removing the co-stimulatory molecules CD80 and CD86 from their surface. Presentation of CD80 and 86 by both Dendritic cells and B-cells is critical for Tfh formation. As a result both Treg depletion and CTLA-4 blockade enhanced vaccine specific antibody production. This means that blocking CTLA-4 may be an effective method to enhance Tfh formation, vaccine responses and combat infection. This work was recently published in the Journal "Immunity" as a featured article. In addition CTLA-4 blockade is currently used as a cancer treatment and my work suggests that anti-tumor antibody responses may also be enhanced in this context.
I also contributed to work demonstrating for the first time that humans with CTLA-4 mutations suffer from severe autoimmunity and that Tregs maintain self-reactive CD8 T-cells in a non-fuctional state characterized by expression CTLA-4.
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[Journal Article] Detection of self-reactive CD8⁺ T cells with an anergic phenotype in healthy individuals.2014
Author(s)
Maeda Y, Nishikawa H, Sugiyama D, Ha D, Hamaguchi M, Saito T, Nishioka M, Wing JB, Adeegbe D, Katayama I, Sakaguchi S.
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Journal Title
Science
Volume: 346
Pages: 1536-40
DOI
Peer Reviewed
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