Human bone marrow hosts polyfunctional memory CD4+ and CD8+ T cells with close contact to IL-15–producing cells

D Herndler-Brandstetter, K Landgraf… - The Journal of …, 2011 - journals.aai.org
D Herndler-Brandstetter, K Landgraf, B Jenewein, A Tzankov, R Brunauer, S Brunner…
The Journal of Immunology, 2011journals.aai.org
Recently, a key role in memory T cell homing and survival has been attributed to the bone
marrow (BM) in mice. In the human BM, the repertoire, function, and survival niches of CD4+
and CD8+ T cells have not yet been elucidated. In this study, we demonstrate that CD4+ and
CD8+ effector memory T cells accumulate in the human BM and are in a heightened
activation state as revealed by CD69 expression. BM-resident memory T cells produce more
IFN-γ and are frequently polyfunctional. Immunofluorescence analysis revealed that CD4+ …
Abstract
Recently, a key role in memory T cell homing and survival has been attributed to the bone marrow (BM) in mice. In the human BM, the repertoire, function, and survival niches of CD4+ and CD8+ T cells have not yet been elucidated. In this study, we demonstrate that CD4+ and CD8+ effector memory T cells accumulate in the human BM and are in a heightened activation state as revealed by CD69 expression. BM-resident memory T cells produce more IFN-γ and are frequently polyfunctional. Immunofluorescence analysis revealed that CD4+ and CD8+ T cells are in the immediate vicinity of IL-15–producing BM cells, suggesting a close interaction between these two cell types and a regulatory role of IL-15 on T cells. Accordingly, IL-15 induced an identical pattern of CD69 expression in peripheral blood CD4+ and CD8+ T cell subsets. Moreover, the IL-15–inducible molecules Bcl-x L, MIP-1α, MIP-1β, and CCR5 were upregulated in the human BM. In summary, our results indicate that the human BM microenvironment, in particular IL-15–producing cells, is important for the maintenance of a polyfunctional memory CD4+ and CD8+ T cell pool.
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