CD69+ memory T lymphocytes of the bone marrow and spleen express the signature transcripts of tissue-resident memory T lymphocytes

Abstract

It is a matter of current debate whether the bone marrow is a hub for circulating memory T lymphocytes and/or the home of resident memory T lymphocytes. Here we demonstrate for CD69⁺ murine CD8⁺ , and CD69⁺ murine and human CD4⁺ memory T lymphocytes of the bone marrow, making up between 30 and 60% of bone marrow memory T lymphocytes, that they express the gene expression signature of tissue-resident memory T lymphocytes. This suggests that a substantial proportion of bone marrow memory T lymphocytes are resident. It adds to previous evidence that bone marrow memory T cells are resting in terms of mobility and proliferation, and maintain exclusive long-term memory to distinct, systemic antigens.

Keywords: Bone marrow; CD69; Memory T cells; Spleen; Tissue-resident signature genes.

Figure 1

CD69 expression of bone marrow and spleen memory T cells defines a transcriptionally distinct population as reported earlier for T_RM cells of other tissues. (A and B) Heatmaps showing reported murine T_RM signature genes of other tissues for CD8 T cells 9, on bone marrow and spleen LCMV‐specific memory CD4⁺ T cells (A) and steady‐state bone marrow memory CD8⁺ T cells (B) isolated from C57BL/6 mice (Supporting Information Fig. 1; 5, 7). n.a., (probes) not present on the arrays, and thus gene expression not analyzed. (C) Heatmap of reported human T_RM signature genes for both CD4⁺ and CD8⁺ T cells of other tissues 8 on human bone marrow and paired peripheral blood (>98% being CD69⁻) memory CD4⁺ T cells according to CD69 expression 3. (D) Principal‐component analysis (PCA) of described murine T_RM signature genes 9 on the cells analyzed in C in comparison with recently activated blood effector/memory CD4⁺ T cells. In A–C, the horizontal and vertical red lines separate up‐ or downregulated genes as described for murine and human T_RM signature genes of other tissues 8, 9. (A) Data shown are from individual mice with a total of three mice from one experiment; (B) data shown are pooled from three independent experiments with cells pooled from 8 to 10 mice per experiment; C/D, data shown were taken from our previously published data GSE50677 3.