Memory CD8+ T cells colocalize with IL‐7+ stromal cells in bone marrow and rest in terms of proliferation and transcription

• Published in: European journal of immunology Vol. 45; no. 4; pp. 975 - 987
• Main Authors: Sercan Alp, Özen, Durlanik, Sibel, Schulz, Daniel, McGrath, Mairi, Grün, Joachim R., Bardua, Marcus, Ikuta, Koichi, Sgouroudis, Evridiki, Riedel, René, Zehentmeier, Sandra, Hauser, Anja E., Tsuneto, Motokazu, Melchers, Fritz, Tokoyoda, Koji, Chang, Hyun‐Dong, Thiel, Andreas, Radbruch, Andreas
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.04.2015; BlackWell Publishing Ltd
• Subjects: Animals; Antigens, CD - biosynthesis; Antigens, Differentiation, T-Lymphocyte - biosynthesis; Bone marrow; Bone Marrow Cells - cytology; Bone Marrow Cells - immunology; CD8 T cell; CD8-Positive T-Lymphocytes - immunology; Cell Proliferation; Gene expression; Highlights; Immunologic Memory - immunology; Interferon-gamma - biosynthesis; Interleukin-2 - biosynthesis; Interleukin-7 - immunology; Interleukin‐7; Ki-67 Antigen - biosynthesis; Lectins, C-Type - biosynthesis; Memory cells; Mice; Mice, Inbred C57BL; Resting Phase, Cell Cycle - immunology; Stromal Cells - immunology; Transcription, Genetic; Tumor Necrosis Factor Receptor Superfamily, Member 9 - biosynthesis; CD8 T cell; Bone marrow; Memory cells; Gene expression; Interleukin-7
• ISSN: 0014-2980; 1521-4141
• DOI: 10.1002/eji.201445295

It is believed that memory CD8+ T cells are maintained in secondary lymphoid tissues, peripheral tissues, and BM by homeostatic proliferation. Their survival has been shown to be dependent on IL‐7, but it is unclear where they acquire it. Here we show that in murine BM, memory CD8+ T cells individually colocalize with IL‐7+ reticular stromal cells. The T cells are resting in terms of global transcription and do not express markers of activation, for example, 4‐1BB (CD137), IL‐2, or IFN‐γ, despite the expression of CD69 on about 30% of the cells. Ninety‐five percent of the memory CD8+ T cells in BM are in G0 phase of cell cycle and do not express Ki‐67. Less than 1% is in S/M/G2 of cell cycle, according to propidium iodide staining. While previous publications have estimated the extent of proliferation of CD8+ memory T cells on the basis of BrdU incorporation, we show here that BrdU itself induces proliferation of CD8+ memory T cells. Taken together, the present results suggest that CD8+ memory T cells are maintained as resting cells in the BM in dedicated niches with their survival conditional on IL‐7 receptor signaling.