| 研究実績の概要 |
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.
|
