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Comment
. 2017 May;101(5):894-895.
doi: 10.1097/TP.0000000000001720.

Epigenetic Remodeling in Exhausted T Cells: Implications for Transplantation Tolerance

Sonia J Laurie  1 , Mandy L Ford
Affiliations
Comment

Epigenetic Remodeling in Exhausted T Cells: Implications for Transplantation Tolerance

Sonia J Laurie et al. Transplantation. 2017 May.
No abstract available

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Conflict of interest statement

Disclosure: The author declares no conflicts of interest.

Figures

Figure 1
Figure 1
Chronic antigen exposure installs enduring and irreversible epigenetic changes with a permanent exhaustion of antigen-specific CD8+ T cells that renders them only partially and temporarily responsive to PD-1 blockade. Following activation, effector T cells express permissive histone marks making their chromatin accessible for remodeling. As high levels of antigen persist, T cells upregulate PD-1 and repressive methylation that accumulates during chronic antigen exposure preventing exhausted cells from responding to checkpoint blockade. Thus, while blockade of PD-1 signaling can transiently restore T cell functionality, the underlying epigenetic landscape of exhausted T cells is not malleable and cannot be altered. Adapted from Hazem E. Ghoneim, H. E., Zamora, A. E., Thomas, P. G., and Youngblood, B. A. Trends in Molecular Medicine, Vol. 22, Issue 12, p1000–1011
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Comment on

  • Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade.
    Pauken KE, Sammons MA, Odorizzi PM, Manne S, Godec J, Khan O, Drake AM, Chen Z, Sen DR, Kurachi M, Barnitz RA, Bartman C, Bengsch B, Huang AC, Schenkel JM, Vahedi G, Haining WN, Berger SL, Wherry EJ. Pauken KE, et al. Science. 2016 Dec 2;354(6316):1160-1165. doi: 10.1126/science.aaf2807. Epub 2016 Oct 27. Science. 2016. PMID: 27789795 Free PMC article.
  • The epigenetic landscape of T cell exhaustion.
    Sen DR, Kaminski J, Barnitz RA, Kurachi M, Gerdemann U, Yates KB, Tsao HW, Godec J, LaFleur MW, Brown FD, Tonnerre P, Chung RT, Tully DC, Allen TM, Frahm N, Lauer GM, Wherry EJ, Yosef N, Haining WN. Sen DR, et al. Science. 2016 Dec 2;354(6316):1165-1169. doi: 10.1126/science.aae0491. Epub 2016 Oct 27. Science. 2016. PMID: 27789799 Free PMC article.

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References

    1. Yang J, Riella LV, Chock S, et al. The novel costimulatory programmed death ligand 1/B7.1 pathway is functional in inhibiting alloimmune responses in vivo. J Immunol. 2011;187(3):1113–1119. - PMC - PubMed
    1. Koehn BH, Ford ML, Ferrer IR, et al. PD-1-dependent mechanisms maintain peripheral tolerance of donor-reactive CD8+ T cells to transplanted tissue. J Immunol. 2008;181(8):5313–5322. - PMC - PubMed
    1. Riella LV, Paterson AM, Sharpe AH, Chandraker A. Role of the PD-1 pathway in the immune response. A J Transplant. 2012;12(10):2575–2587. - PMC - PubMed
    1. Pauken KE, Sammons MA, Odorizzi PM, et al. Epigenetic stability of exhausted T cells limits durability of reinvigoration by PD-1 blockade. Science. 2016;354(6316):1160–1165. - PMC - PubMed
    1. Sen DR, Kaminski J, Barnitz RA, et al. The epigenetic landscape of T cell exhaustion. Science. 2016;354:1165–1169. - PMC - PubMed

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