id author title date pages extension mime words sentences flesch summary cache txt cord-103517-1itisiup Kwesi-Maliepaard, Eliza Mari The histone methyltransferase DOT1L prevents antigen-independent differentiation and safeguards epigenetic identity of CD8+ T cells 2019-11-18 .txt text/plain 7875 419 54 T-cell specific ablation of Dot1L resulted in loss of naïve CD8+ T cells and premature differentiation towards a memory-like state, independent of antigen exposure and in a cell-intrinsic manner. Mechanistically, DOT1L controlled T-cell differentiation and function by ensuring normal T-cell receptor density and signaling, and by maintaining epigenetic identity, in part by indirectly supporting the repression of developmentally-regulated genes. Analysis of CD8 + T cell subsets in the spleen revealed that Dot1L-KO mice showed a severe loss of naïve (CD44 -CD62L + ) CD8 + T (T N ) cells which was linked to a massive gain of the CD44 + CD62L + phenotype, a feature of central memory T cells (T CM ; Fig. 1A -B). To determine whether peripheral T AIM cells observed in the Dot1L-KO setting originate intrathymically, as reported previously for IL-4 dependent innate memory T cells 3 , we compared RNA-Seq data from SP CD8 + thymocytes from KO and WT mice. ./cache/cord-103517-1itisiup.txt ./txt/cord-103517-1itisiup.txt