Oct1 and OCA-B are selectively required for CD4 memory T cell function.

J Exp Med
Authors
Keywords
Abstract

Epigenetic changes are crucial for the generation of immunological memory. Failure to generate or maintain these changes will result in poor memory responses. Similarly, augmenting or stabilizing the correct epigenetic states offers a potential method of enhancing memory. Yet the transcription factors that regulate these processes are poorly defined. We find that the transcription factor Oct1 and its cofactor OCA-B are selectively required for the in vivo generation of CD4(+) memory T cells. More importantly, the memory cells that are formed do not respond properly to antigen reencounter. In vitro, both proteins are required to maintain a poised state at the Il2 target locus in resting but previously stimulated CD4(+) T cells. OCA-B is also required for the robust reexpression of multiple other genes including Ifng. ChIPseq identifies ∼50 differentially expressed direct Oct1 and OCA-B targets. We identify an underlying mechanism involving OCA-B recruitment of the histone lysine demethylase Jmjd1a to targets such as Il2, Ifng, and Zbtb32. The findings pinpoint Oct1 and OCA-B as central mediators of CD4(+) T cell memory.

Year of Publication
2015
Journal
J Exp Med
Volume
212
Issue
12
Pages
2115-31
Date Published
2015 Nov 16
ISSN
1540-9538
URL
DOI
10.1084/jem.20150363
PubMed ID
26481684
PubMed Central ID
PMC4647264
Links
Grant list
R01 AI100873 / AI / NIAID NIH HHS / United States
R01AI100873 / AI / NIAID NIH HHS / United States
Howard Hughes Medical Institute / United States