Characterization of donor and recipient CD8+ tissue-resident memory T cells in transplant nephrectomies

Abstract

Tissue-resident memory T (T RM ) cells are characterized by their surface expression of CD69 and can be subdivided in CD103+ and CD103− T RM cells. The origin and functional characteristics of T RM cells in the renal allograft are largely unknown. To determine these features we studied T RM cells in transplant nephrectomies. T RM cells with a CD103+ and CD103− phenotype were present in all samples ( n = 13) and were mainly CD8+ T cells. Of note, donor-derived T RM cells were only detectable in renal allografts that failed in the first month after transplantation. Grafts, which failed later, mainly contained recipient derived T RM cells. The gene expression profiles of the recipient derived CD8+ T RM cells were studied in more detail and showed a previously described signature of tissue residence within both CD103+ and CD103− T RM cells. All CD8+ T RM cells had strong effector abilities through the production of IFNγ and TNFα, and harboured high levels of intracellular granzyme B and low levels of perforin. In conclusion, our results demonstrate that donor and recipient T RM cells reside in the rejected renal allograft. Over time, the donor-derived T RM cells are replaced by recipient T RM cells which have features that enables these cells to aggressively respond to the allograft.

Human intestinal tissue-resident memory T cells comprise transcriptionally and functionally distinct subsets

“…As expected, the genes downregulated in CD69 + T cells were either not detected or were found at low levels in both clusters ( Figures S2 D and S2E). However, several T RM cell-associated genes upregulated in CD69 + T cells were differentially expressed between the two clusters, with population 1 expressing more ITGAE and ITGA1 (in agreement with work on renal T RM cells [ de Leur et al., 2019 ]), and population 2 expressing more CRTAM ( Figures 2 D, 2F, and S2 F). T cell receptor (TCR) repertoire analysis revealed the presence of shared clonotypes between the two T RM clusters ( Figure S2 G).…”

Immune cell composition in normal human kidneys

“…A previous study reported that donor T cells were associated with the transplant outcome of lungs 33 , and therefore the presence or abundance of donor T cells may be related to kidney transplant outcome. A previous study identified the presence of donor-derived CD8 + T RM cells was associated with graft failure in the first month after transplantation 34 . Additionally, an abundance of T cells may affect the surveillance of kidney cancers because this cancer type is typically immunogenic and T cell-dependent 35 .…”

Differential effects of heat-inactivated, secretome-deficient MSC and metabolically active MSC in sepsis and allogenic heart transplantation

“…Patients experiencing cardiac allograft rejection show distinct changes in CD4 + and CD8 + T‐cell subsets in peripheral blood samples . In the process of allograft rejection, donor‐derived tissue‐resident CD8 + T‐cells become gradually replaced by alloreactive, recipient‐derived CD8 + T‐cells with strong effector abilities and high levels of intracellular granzyme B . Through staining of CD3 + T‐cells in the rejected hearts, we demonstrated that graft rejection in our model was clearly accompanied by T‐cell infiltration.…”

“…The in vitro model, where MSCs, but not HI‐MSCs suppressed CD3 + T‐cell proliferation provided mechanistic insights into the differential effects of MSCs and HI‐MSCs in T‐cell‐mediated allograft rejection. We revealed that only MSCs are able to suppress the granzyme B‐mediated cytotoxic CD8 + T‐cell response, which is known as one of the principal mediators of acute allograft rejection . MSCs have been shown to suppress T‐cell proliferation and shift the effector functions of T‐cells toward regulatory functions, mainly through the expression of immunomodulatory molecules such as IDO, and secretion of prostaglandin‐E2 (PGE2), nitric oxide, and TGF‐β .…”