-
Views
-
Cite
Cite
Dean R Tantin, Keiji Zhao, Matthew A Williams, J Scott Hale, Binbin Lai, Gang Ren, Heejoo Kim, Transcription coactivator OCA-B mediates interactions between target loci in T cells and is sufficient to promote CD4 memory in vivo, The Journal of Immunology, Volume 202, Issue 1_Supplement, May 2019, Page 186.3, https://doi.org/10.4049/jimmunol.202.Supp.186.3
Close - Share Icon Share
Abstract
Stable epigenetic changes occurring during T cell activation are crucial for the generation of immunological memory. In CD4 T cells, OCA-B (Pou2af1/OBF-1/Bob.1) promotes poised gene expression states in an array of direct immunomodulatory target genes (e.g. Il2, Il21 and Ifng) via the recruitment of the histone lysine demethylase Jmjd1a/Kdm3a. Our prior work indicates that OCA-B is not expressed in naïve CD4 T cells, but becomes stably expressed upon persistent antigen exposure. OCA-B is also critical for the generation of functional CD4 memory T cells in response to pathogen infection. By ectopically expressing OCA-B in SMARTA TCR transgenic T cells and co-transferring transduced T cells together with empty vector controls, we show that OCA-B does not affect primary effector responses, but is sufficient to promote formation of long-lived memory T cells. Although there are no differences in T cell numbers or function, the promotion of memory is preceded in the effector phase by changes in the expression of surface markers such as CD62L, ICOS and PD-1. We identify a mode of transcription regulation by OCA-B in T cells in which OCA-B facilitates communication between target loci such as Il2 and Il21. These results indicate that expressing OCA-B may be useful as a method of enhancing CD4 memory.
