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. 2019 Jul 31;8:F1000 Faculty Rev-1278. [Version 1] doi: 10.12688/f1000research.18211.1

Figure 3. An integrated model of memory CD8 T-cell differentiation.

Figure 3.

( A) Individual naïve CD8 T cells undergo memory CD8 T-cell programming wherein they acquire fundamental traits of fully developed memory CD8 T cells prior to the first cell division. ( B) The growing nascent CD8 T-cell population comprises a transitional population of effector and memory precursor progenitor (EMPpro) cells that are metastable at the chromatin and transcriptional level and can give rise to all subsets of differentiated CD8 T-cell progeny. ( C) A small number of EMPpro cells randomly undergo massive proliferation coupled to higher expression of multiple transcription factors (TFs) in response to inflammatory signals that drive transcription underlying the phenotypic and functional profiles of terminally differentiated CD8 T cells. ( D) Multiple chromatin regulatory factors that methylate DNA and histones persistently repress genes that otherwise favor quiescence, lymphoid retention, and overall “stemness” and thus enforce terminal differentiation. Factors generally associated with terminal CD8 T-cell differentiation (red) and memory (blue) are highlighted by color but are not intended to imply exclusive correlations.