Journal
NATURE IMMUNOLOGY
Volume 20, Issue 3, Pages 337-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41590-018-0311-z
Keywords
-
Categories
Funding
- Intramural Research Program of the US National Institutes of Health, National Cancer Institute, Center for Cancer Research [ZIABC011480]
- US National Institutes of Health [GM100776, CA85842]
- Wellcome Trust/Royal Society [105663/Z/14/Z]
- UK Biotechnology and Biological Sciences Research Council [BB/N007794/1]
- Cancer Research UK [C52623/A22597]
- Wellcome Trust [105663/Z/14/Z] Funding Source: Wellcome Trust
- BBSRC [BBS/E/B/000C0428, BBS/E/B/000C0427, BBS/E/B/000C0409, BB/N007794/1, 1642652, BBS/E/B/000C0407] Funding Source: UKRI
- MRC [MR/S024468/1, 1947452, MC_UP_1502/3] Funding Source: UKRI
- NATIONAL CANCER INSTITUTE [ZIABC011633] Funding Source: NIH RePORTER
Ask authors/readers for more resources
Stem cells are maintained by transcriptional programs that promote self-renewal and repress differentiation. Here, we found that the transcription factor c-Myb was essential for generating and maintaining stem cells in the CD8(+) T cell memory compartment. Following viral infection, CD8(+) T cells lacking Myb underwent terminal differentiation and generated fewer stem cell-like central memory cells than did Myb-sufficient T cells. c-Myb acted both as a transcriptional activator of Tcf7 (which encodes the transcription factor Tcf1) to enhance memory development and as a repressor of Zeb2 (which encodes the transcription factor Zeb2) to hinder effector differentiation. Domain-mutagenesis experiments revealed that the transactivation domain of c-Myb was necessary for restraining differentiation, whereas its negative regulatory domain was critical for cell survival. Myb overexpression enhanced CD8(+) T cell memory formation, polyfunctionality and recall responses that promoted curative antitumor immunity after adoptive transfer. These findings identify c-Myb as a pivotal regulator of CD8(+) T cell stemness and highlight its therapeutic potential.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available