Surface CD69-negative bone-marrow resident human memory T cells [ESR transcription]

Across tissues, tissue-resident memory T cells have been defined as cells which express CD69 in their cell surface, but not S1PR1, the receptor for the tissue-egress signal sphingosin-1-phosphate (S1P). It is less clear whether CD69-negative memory T cells are also tissue-resident. Here, we compare transcriptomes and T cell receptor repertoires of individual CD4 and CD8 memory T cells from paired blood and bone marrow of three human donors. CD69- memory T cells of blood and bone marrow share transcriptionally defined clusters, as defined by signature genes reflecting their imprinting during activation. However, cells of related clusters of blood and bone marrow have distinct TCR repertoires, suggesting that they represent distinct compartments of memory, and that the CD69- memory T cells are residents of the bone marrow. Interestingly, the surface CD69- memory T cells of bone marrow do transcribe the CD69 gene, and they express S1PR1, suggesting that they are blindfolded for S1P by dimerization and internalization of CD69 and S1PR1, maintaining them in the tissue. Ex vivo transcriptome and TCR of paired blood and bone marrow memory T cells in the resting state