IL-15-dependent upregulation of GITR on CD8 memory phenotype T cells in the bone marrow relative to spleen and lymph node suggests the bone marrow as a site of superior bioavailability of IL-15

The Journal of Immunology : Official Journal of the American Association of Immunologists
Laura M SnellTania H Watts

Abstract

CD8 memory T cells are enriched in the bone marrow, a site where these cells are thought to receive homeostatic signals. However, the primary site where CD8 memory T cells receive their cytokine-induced homeostatic signals has recently come under debate. In this study, we demonstrate that the bone marrow contains a fraction of CD8 memory phenotype T cells with elevated expression of glucocorticoid-induced TNFR-related protein (GITR). In contrast, splenic and lymph node memory phenotype T cells have GITR levels similar to those on naive T cells. The bone marrow GITR(hi) memory T cells have a phenotype indicative of cytokine activation, with higher CD122 and lower CD127 than do the GITR(basal) memory T cells. Remarkably, these bone marrow-specific GITR(hi) cells are almost completely ablated in the absence of IL-15, whereas TNFR2 and 4-1BB expression on the CD8 memory T cells are IL-15 independent. Furthermore, adoptively transferred splenic CD8 memory phenotype T cells show IL-15-dependent GITR upregulation upon entry into the bone marrow. This result implies that the selective appearance of GITR(hi) memory phenotype T cells in the bone marrow reflects the local microenvironment rather than a different subset of memory T cells. ...Continue Reading

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Feb 26, 2016·Frontiers in Immunology·Francesca Di Rosa, Thomas Gebhardt
Nov 21, 2014·Journal for Immunotherapy of Cancer·Michael J McNamaraWilliam L Redmond
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Dec 27, 2016·Frontiers in Immunology·Francesca Di Rosa, Tania H Watts
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Apr 13, 2021·Frontiers in Molecular Biosciences·Fabrizio MatteiGiovanna Schiavoni

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