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

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 G ₀ phase of cell cycle and do not express Ki-67. Less than 1% is in S/M/G ₂ 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.