Background: At border sites, and in internal organs, tissue resident memory T cells (T-RM) contribute to the immune barrier against pathogens like viruses, bacteria, fungi, and cancer. However,... Show moreBackground: At border sites, and in internal organs, tissue resident memory T cells (T-RM) contribute to the immune barrier against pathogens like viruses, bacteria, fungi, and cancer. However, information on the presence and function of these cells in the human kidney is scant. In order to better understand the T cell-mediated immunological defense in this organ, we aimed to determine phenotypic and functional aspects of CD8 and CD4 T cells present in healthy and allograft kidney tissue. Methods: Using multichannel flow cytometry, we assessed the phenotype and function of T cells in healthy renal tissue samples (n = 5) and kidney allograft tissue (n = 7) and compared these aspects to T cells in peripheral blood from healthy controls (n = 13). Results: Kidney tissue samples contained substantial amounts of CD8 and CD4 T cells. In contrast to the circulating cells, kidney T cells frequently expressed CD69 and CD103, and were more often actively cycling. Furthermore, nearly all kidney T cells expressed CXCR3, and often expressed CXCR6 compared to T cells in the circulation. Markedly, kidney T cells produced greater quantities of IFN gamma than circulating cells and were frequently polyfunctional. Conclusion: Functional T cells with the characteristic traits of T-RM reside in human kidney tissues. These cells are more often actively cycling and frequently express CXCR3 and CXCR6. Show less
BM has been put forward as a major reservoir for memory CD8(+) T cells. In order to fulfill that function, BM should "store" memory CD8(+) T cells, which in biological terms would require these ... Show moreBM has been put forward as a major reservoir for memory CD8(+) T cells. In order to fulfill that function, BM should "store" memory CD8(+) T cells, which in biological terms would require these "stored" memory cells to be in disequilibrium with the circulatory pool. This issue is a matter of ongoing debate. Here, we unequivocally demonstrate that murine and human BM harbors a population of tissue-resident memory CD8(+) T (T-RM) cells. These cells develop against various pathogens, independently of BM infection or local antigen recognition. BM CD8(+) T-RM cells share a transcriptional program with resident lymphoid cells in other tissues; they are polyfunctional cytokine producers and dependent on IL-15, Blimp-1, and Hobit. CD8(+) T-RM cells reside in the BM parenchyma, but are in close contact with the circulation. Moreover, this pool of resident T cells is not size-restricted and expands upon peripheral antigenic re-challenge. This works extends the role of the BM in the maintenance of CD8(+) T cell memory to include the preservation of an expandable reservoir of functional, non-recirculating memory CD8(+) T cells, which develop in response to a large variety of peripheral antigens. Show less