Methylomes of human CD4 and CD8 memory T lymphocytes reveal tissue-specific epigenetic signatures for maintenance and recall function

|
Xiangyi Deng, Weijie Du, Gilles Gasparoni, Abdulrahman Salhab, Karl Nordström, Jinchan Li, Viktoria Wagner, Erping Zhang, Joachim Wachtlin, Juliane Bodo, Simon Reinke, Hong Lei, Carsten Perka, Sebastian Hardt, Thomas Dörner, Christoph Holmer, Mario Tönnies, Torsten Bauer, Hyun-Dong Chang, Julia K Polansky, Jörn Walter, Pawel Durek, Andreas Radbruch, Jun Dong

Immun Inflamm. 2025;1(1):13. doi: 10.1007/s44466-025-00009-x. Epub 2025 Oct 1.

ABSTRACT

Adaptive immunity relies on antibodies and memory B and T cells, with memory T cells providing "reactive memory". These cells either circulate in the blood or remain as tissue-resident memory T cells, yet the epigenetic mechanisms underlying their recall function and maintenance are not well understood. Here, we present a comprehensive analysis of 56 reduced representation bisulfite sequencing (RRBS) datasets from 22 memory CD4 and CD8 T-cell populations isolated from human bone marrow, intestine, spleen, lung, skin, and peripheral blood, including surface CD69-positive and CD69-negative cells. Our study reveals unique DNA hypomethylation patterns in tissue-resident memory T cells, particularly in regions associated with genes involved in tissue homing, residency, and transcription factors regulating recall effector memory. The methylomes and differential methylation signatures identified here serve as a valuable resource for understanding the epigenetic program of memory T lymphocytes, their roles in immunological recall, and their maintenance within specific tissues.

SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s44466-025-00009-x.

PMID:41262706 | PMC:PMC12623507 | DOI:10.1007/s44466-025-00009-x