Heterologous Immunity of Virus-Specific T Cells Leading to Alloreactivity: Possible Implications for Solid Organ Transplantation

Karahan, Gonca E.; Claas, Frans H.J.; Heidt, Sebastiaan

doi:10.3390/v13122359

Cited by 10 publications

(6 citation statements)

References 84 publications

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“…Last, cross-reactivity of influenza A–specific T RM cells against other locally present antigens within the kidney may also occur ( 37 , 38 ). Whether influenza A–specific T RM cells exist in other solid organs except the lungs is unknown ( 25 ).…”

Section: Discussionmentioning

confidence: 99%

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

Hullegie-Peelen,

Tejeda Mora,

Hesselink

et al. 2023

JCI Insight

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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.

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Section: Discussionmentioning

confidence: 99%

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

Hullegie-Peelen,

Tejeda Mora,

Hesselink

et al. 2023

JCI Insight

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“…Due to the inherent capacity of T‐cell receptors to cross‐react with multiple antigens, polyclonal memory T‐cell activation following viral infection is not uncommon. The latter comprised a broad range of T cells expressing viral related and unrelated peptides commonly refer to as heterologous immunity 35–38 . Therefore, the many viruses encountered throughout life could induce a broad repertoire of donor‐specific alloreactive memory T cells pool already in place at the time of transplantation.…”

Section: Discussionmentioning

confidence: 99%

“…The latter comprised a broad range of T cells expressing viral related and unrelated peptides commonly refer to as heterologous immunity. [35][36][37][38] Therefore, the many viruses encountered throughout life could induce a broad repertoire of donor-specific alloreactive memory T cells pool already in place at the time of transplantation. CMV and EBV in particular are known for inducing public TCR responses.…”

Section: Discussionmentioning

confidence: 99%

Severe delayed graft function in a living‐related kidney transplant recipient due to combination of alloimmunity, autoimmunity, and heterologous immunity: A case report

Attas

Alshami

Mohamed

et al. 2022

Pediatric Transplantation

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Background Delayed graft function is a manifestation of acute kidney injury unique to transplantation usually related to donor ischemia or recipient immunological causes. Ischemia also considered the most important trigger for innate immunity activation and production of non‐HLA antibodies. While ischemia is inevitable after deceased donor transplantation, this complication is rare after living transplantation. Heterologous Immunity commonly used to describe the activation of T cells recognizing specific pathogen‐related antigens as well unrelated antigens is common post‐viral infection. In transplant‐setting induction of heterologous immunity that cross‐react with HLA‐antigens and subsequent reactivation of memory T cells can lead to allograft rejection. Methods Here we describe a non‐sensitized child with ESRD secondary to lupus nephritis and recent history of COVID‐19 infection who experienced 17 days of anuria after first kidney living transplantation from her young HLA‐haploidentical uncle donor. Graft histology showed acute cellular rejection, evidence of mild antibody‐mediated rejection and vascular wall necrosis in some arterioles suggesting possibility of intraoperative graft ischemia. Both pre‐ and post‐transplant sera showed very high level of several non‐HLA antibodies. Results The patient was treated for cellular and antibody‐mediated rejection while maintained on hemodialysis before her graft function started to improve on day seventeen post transplantation. Conclusion The cellular rejection likely trigged by ischemia that activated T‐cells‐mediated immunity. The high level of non‐ HLA‐antibodies further aggravated the damage and the rapid onset of rejection may be partly related to memory T‐cell activation induced by heterologous immunity.

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“…It has been hypothesized that this is because effects will be more likely to be present at the time of active viral infections, so follow-up studies should address heterologous immunity in that context. 169 Another possibility is that the cross-reactive T cells are blocked from responding to the allograft by regulatory cells, potentially even regulatory T cells with the same TCR. It is also possible that the immunosuppression in the transplant recipients in these studies was adequate to block activity by these cross-reactive T cells.…”

Section: Heterologous Immunitymentioning

confidence: 99%

Infection, Rejection, and the Connection

Higdon

Tan

2022

Transplantation

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Solid organ transplantation is a life-saving treatment for people with end-stage organ disease. Immune-mediated transplant rejection is a common complication that decreases allograft survival. Although immunosuppression is required to prevent rejection, it also increases the risk of infection. Some infections, such as cytomegalovirus and BK virus, can promote inflammatory gene expression that can further tip the balance toward rejection. BK virus and other infections can induce damage that resembles the clinical pathology of rejection, and this complicates accurate diagnosis. Moreover, T cells specific for viral infection can lead to rejection through heterologous immunity to donor antigen directly mediated by antiviral cells. Thus, viral infections and allograft rejection interact in multiple ways that are important to maintain immunologic homeostasis in solid organ transplant recipients. Better insight into this dynamic interplay will help promote long-term transplant survival.

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Heterologous Immunity of Virus-Specific T Cells Leading to Alloreactivity: Possible Implications for Solid Organ Transplantation

Cited by 10 publications

References 84 publications

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

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

Severe delayed graft function in a living‐related kidney transplant recipient due to combination of alloimmunity, autoimmunity, and heterologous immunity: A case report

Infection, Rejection, and the Connection

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