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A8.10 Human memory t cells from the bone marrow are resting and maintain long-lasting memory
  1. Anna Okhrimenko1,
  2. Joachim R. Grün2,
  3. Kerstin Westendorf1,
  4. Zhuo Fang3,
  5. Simon Reinke4,
  6. Philipp von Roth5,
  7. Georgi Wassilew5,
  8. Anja A. Kühl6,
  9. Robert Kudernatsch7,
  10. Sonya Demski7,
  11. Carmen Scheibenbogen7,
  12. Koji Tokoyoda8,
  13. Mairi A McGrath1,
  14. Martin Raftery9,
  15. Alessandro Serra1,
  16. Hyun-Dong Chang1,
  17. Andreas Radbruch1,*,
  18. Jun Dong1,*
  1. 1Cell Biology, Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, Germany
  2. 2Bioinformatics, Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, Germany
  3. 3Signal Transduction, Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, Germany
  4. 4Core Unit Cell Harvesting, Berlin-Brandenburg Center for Regenerative Therapies, Charité University of Medicine Berlin, Germany
  5. 5Center for Musculoskeletal Surgery, Charité University of Medicine Berlin, Germany
  6. 6Infectiology & Rheumatology, Charité University of Medicine Berlin, Germany
  7. 7Clinical Tumor Immunology & Immunemonitoring, Institute for Medical Immunology, Charité University of Medicine Berlin; Germany
  8. 8Osteoimmunology, Deutsches Rheuma-Forschungszentrum (DRFZ) Berlin, Germany
  9. 9Institute of Virology, Charité University of Medicine Berlin, Germany
  10. *Equal contribution

Abstract

Objectives Memory T cells are essential components of immunological memory, but little is known about their maintenance. Recirculating memory T cells of blood and secondary lymphoid organs slowly decay in numbers. In mice, we have recently identified professional resting memory CD4+ T cells located in the BM and stably maintained in dedicated survival niches. The cells are resting, despite expression of CD69. Here we analyse and compare paired human peripheral blood (PB) and BM samples for phenotype, specificity and cytokine profiles of memory CD4+ and CD8+ T cells.

Material and Methods Mononuclear cells were isolated from paired PB and BM samples from individuals undergoing hip replacement surgery. Phenotypic analysis and cytokine profile of memory T-cells in response to CMV pp65, tetanus toxoid and measles were measured by flow cytometry. Proliferation and cell cycle status were analysed using Ki-67 and propidium iodide staining, respectively. Global transcription of cells was assessed by microarray analysis.

Results Significantly higher numbers of memory T cells were found in BM than in PB. BM memory T cells displayed polyfunctionality, secreted a multitude of cytokines, and specificities for all recall antigens tested. They maintained long-lasting memory, even when it was not detectable in blood. CD69-expressing memory T cells were detected in BM but not in PB. Ki-67- and propidium iodide-positive cells were significantly lower in CD69+ memory T cells from BM compared to PB. BM CD69+ memory T cells showed a resting global gene expression profile.

Conclusions BM is home to resting, professional memory CD4+ and CD8+T cells, providing systemic, stable longterm memory.

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