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Eur J Immunol ; 45(4): 975-87, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25639669

ABSTRACT

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.


Subject(s)
Bone Marrow Cells/cytology , CD8-Positive T-Lymphocytes/immunology , Immunologic Memory/immunology , Resting Phase, Cell Cycle/immunology , Stromal Cells/immunology , Animals , Antigens, CD/biosynthesis , Antigens, Differentiation, T-Lymphocyte/biosynthesis , Bone Marrow Cells/immunology , Cell Proliferation , Interferon-gamma/biosynthesis , Interleukin-2/biosynthesis , Interleukin-7/immunology , Ki-67 Antigen/biosynthesis , Lectins, C-Type/biosynthesis , Mice , Mice, Inbred C57BL , Transcription, Genetic , Tumor Necrosis Factor Receptor Superfamily, Member 9/biosynthesis
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