CD8 memory

CD8 memory

1. Memory T cell differentiation models

   • Progressive differentiation (Tscm)
     • Cieri, N. et al. Generation of human memory stem T cells after haploidentical T-replete hematopoietic stem cell transplantation. Blood125, 2865–2874 (2015). -----------> Notably, only naive T cells and TSCM cells were able to reconstitute the entire heterogeneity of memory T cell subsets, including TSCMcells33. A fraction of cells originally designated as TEM cells reverted to a TCM cell phenotype33. By contrast, only a very limited number of TCM and TEM cells converted to the TSCM cell type.
     • Oliveira, G. et al. Tracking genetically engineered lymphocytes long-term reveals the dynamics of T cell immunological memory.Sci. Transl. Med.7, 317ra198 (2015) --------> It was thus possible to show that dominant T cell clones detected long-term originate preferentially from infused TSCM cells, and to a lesser degree, from TCM clones.
     • Fuertes Marraco, S.A. et al. Long-lasting stem cell-like memory CD8+ T cells with a naive-like profile upon yellow fever vaccination. Sci. Transl. Med.7, 282ra48 (2015) --------> YF-specific TSCMcells were detectable at early time points after vaccination when the immune response was dominated by effector T cells.
   • Assymetric division
     • The asymmetric theory can pottentialy unify both the progressive thepry and the de-differentiation therpy (I think)
     • Nish, S.A., Zens, K.D., Kratchmarov, R., Lin, W.-H.W., Adams, W.C., Chen, Y.-H., Yen, B., Rothman, N.J., Bhandoola, A., Xue, H.-H., et al. (2017). CD4+ T cell effector commitment coupled to self-renewal by asymmetric cell divisions. J. Exp. Med. 214, 39–47.
   • De-differentiation from effectors
     • Youngblood, B., Hale, J.S., Kissick, H.T., Ahn, E., Xu, X., Wieland, A., Araki, K., West, E.E., Ghoneim, H.E., Fan, Y., et al. (2017). Effector CD8 T cells dedifferentiate into long-lived memory cells. Nature.
     • Akondy, R.S., Fitch, M., Edupuganti, S., Yang, S., Kissick, H.T., Li, K.W., Youngblood, B.A., Abdelsamed, H.A., McGuire, D.J., Cohen, K.W., et al. (2017). Origin and differentiation of human memory CD8 T cells after vaccination. Nature.
     • Bannard, O., Kraman, M., and Fearon, D.T. (2009). Secondary replicative function of CD8+ T cells that had developed an effector phenotype. Science 323, 505–509.

2. Subpopulations

   • image from Gattinoni, Nature Medicine, 2017
   • Naive
     • CD45RA+ CD45ROneg CCR7+ CD62L+ CD28+ CD27+ IL7Ra+ CXCR3neg CD95neg CD11aneg IL2Rbneg CD58neg CD57neg 
   • Tscm
     • CD45RA+ CD45ROneg CCR7+ CD62L+ CD28+ CD27+ IL7Ra+ CXCR3+ CD95+ CD11a+ IL2Rb+ CD58+ CD57neg
   • Tcm
     • CD45RAneg CD45RO+ CCR7+ CD62L+ CD28+ CD27+ IL7Ra+ CXCR3+ CD95+ CD11a+ IL2Rb+ CD58+ CD57neg
   • Tem
     • CD45RAneg CD45RO+ CCR7neg CD62Lneg CD28+/- CD27+/- IL7Ra+/- CXCR3neg CD95+ CD11a+ IL2Rb+ CD58+ CD57+/-
   • effector
     • CD45RA+ CD45ROneg CCR7neg CD62Lneg CD28neg CD27neg IL7Raneg CXCR3neg CD95+ CD11a+ IL2Rb+ CD58+ CD57+

3. figuras from Gattinoni, 2012 nat rev cancer

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