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

Eur J Immunol. 2015 Apr;45(4):975-87. doi: 10.1002/eji.201445295. Epub 2015 Feb 27.

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.

Keywords: Bone marrow; CD8 T cell; Gene expression; Interleukin-7; Memory cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

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

Substances

  • Antigens, CD
  • Antigens, Differentiation, T-Lymphocyte
  • CD69 antigen
  • Interleukin-2
  • Interleukin-7
  • Ki-67 Antigen
  • Lectins, C-Type
  • Mki67 protein, mouse
  • Tumor Necrosis Factor Receptor Superfamily, Member 9
  • Interferon-gamma