Virus-specific TRM cells of both donor and recipient origin reside in human kidney transplants

Abstract

Tissue-resident lymphocytes (TRLs) are critical for local protection against viral pathogens in peripheral tissue. However, it is unclear if TRLs perform a similar role in transplanted organs under chronic immunosuppressed conditions. In this study, we aimed to characterize the TRL compartment in human kidney transplant nephrectomies and examine its potential role in antiviral immunity. The TRL compartment of kidney transplants contained diverse innate, innate-like, and adaptive TRL populations expressing the canonical residency markers CD69, CD103, and CD49a. Chimerism of donor and recipient cells was present in 43% of kidney transplants and occurred in all TRL subpopulations. Paired single-cell transcriptome and T cell receptor (TCR) sequencing showed that donor and recipient tissue–resident memory T (T RM ) cells exhibit striking similarities in their transcriptomic profiles and share numerous TCR clonotypes predicted to target viral pathogens. Virus dextramer staining further confirmed that CD8 T RM cells of both donor and recipient origin express TCRs with specificities against common viruses, including CMV, EBV, BK polyomavirus, and influenza A. Overall, the study results demonstrate that a diverse population of TRLs resides in kidney transplants and offer compelling evidence that T RM cells of both donor and recipient origin reside within this TRL population and may contribute to local protection against viral pathogens.

Tissue-resident Lymphocytes Are Released During Hypothermic and Normothermic Machine Perfusion of Human Donor Kidneys

“… 15 However, given their low proportion in perfusates compared with tissue, the impact of TRL release remains uncertain. 14 …”

“…TRLs constitute a diverse group of cells residing in nonlymphoid tissues like kidneys and play a key role in local immune surveillance. 13 , 14 TRLs are characterized by the expression of specific residency markers, such as CD69, CD103, and CD49a. 14 , 15 Their release in perfusates is intriguing concerning their usual residency within tissue and might be a response to cellular stress or tissue injury.…”

“… 13 , 14 TRLs are characterized by the expression of specific residency markers, such as CD69, CD103, and CD49a. 14 , 15 Their release in perfusates is intriguing concerning their usual residency within tissue and might be a response to cellular stress or tissue injury. Consequently, exploring TRL prevalence in donor kidney perfusates could provide a noninvasive approach to assess organ viability pretransplantation.…”