Adaptive Immunity Rather Than Viral Cytopathology Mediates Polyomavirus-Associated Nephropathy in Mice

Albrecht, J.; Dong, Ying; Wang, J.; Breeden, Cynthia; Farris, Alton B.; Lukacher, Aron E.; Newell, Kenneth A.

doi:10.1111/j.1600-6143.2012.04005.x

Cited by 12 publications

(21 citation statements)

References 47 publications

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“…In a mouse model of kidney transplantation, mouse polyoma virus infection was also shown to enhance anti-donor immunity (23). Moreover, graft nephropathy did not correlate with viral load suggesting that the mechanism for renal injury is not direct viral cytopathology but more likely the interplay between the infection and the alloimmune response (24). In patients, infections have also been associated with episodes of acute rejection.…”

Section: Infections and Alloimmunitymentioning

confidence: 99%

Microbes and Allogeneic Transplantation

2014

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Summary Microbial products can be recognized by pattern recognition receptors (PRRs) expressed by immune and parenchymal cells and drive innate immunity that can in turn shape adaptive immune responses to microbial and transplant antigens. In transplanted patients, the signals and their downstream inflammatory cytokines elicited in response to infections can modulate ongoing alloimmune responses and modify the fate of transplanted organs. In recent years, it has become apparent that microbial signals can be generated not only by active pathogenic infections, but also by commensal microbiota thus opening a new field of research into the interplay between the microbiota and the immune system in homeostasis and disease. The wide use of antibiotics and immunosuppressive drugs in transplanted patients can have dramatic consequences on the microbiota that can, in turn, shape immune responses and perhaps alloresponses, whereas the ongoing immune responses can in turn affect the commensal or pathogenic microorganisms in a feed-forward circle. Here, we discuss known and hypothesized mechanisms for how infections or microbiota-derived signals may affect local or systemic alloimmunity and briefly review data on downstream effects of antibiotics and vaccinations.

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Section: Infections and Alloimmunitymentioning

confidence: 99%

Microbes and Allogeneic Transplantation

2014

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“…Kidney transplants were performed in 8- to 12-week-old male mice as previously described. 32 There were no significant differences in perioperative mortality between groups, and overall surgical mortality was less than 10%. All transplanted mice were observed for 48 hours after transplant to monitor for immediate complications from surgical technique.…”

Section: Methodsmentioning

confidence: 78%

“…31 Further studies in this model revealed that the adaptive immune response, and not viral cytopathology, was responsible for rejection. 32 These studies established the relationship between alloimmunity and local PyV-mediated allograft injury.…”

mentioning

confidence: 98%

Alloimmunity But Not Viral Immunity Promotes Allograft Loss in a Mouse Model of Polyomavirus-Associated Allograft Injury

Kim

Wang

Dong

et al. 2017

Transplantation Direct

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BackgroundThe interplay between viral infection and alloimmunity is known to influence the fate of transplanted organs. Clarifying how local virus-associated inflammation/injury and antiviral immunity can alter host alloimmune responses in transplantation remains a critical question.MethodsWe used a mouse model of polyomavirus (PyV) infection and kidney transplantation to investigate the roles of direct viral pathology, the antiviral immune response, and alloimmunity in the pathogenesis of PyV-associated allograft injury. We have previously shown that an effective primary T cell response is required in PyV-associated graft injury.ResultsHere we show that the transfer of primed antidonor, but not antiviral, T cells results in PyV-associated allograft injury. In further studies, we use a surrogate minor antigen model (ovalbumin) and show that only antidonor specific T cells and not antiviral specific T cells are sufficient to mediate injury. Lastly, we demonstrate that local but not systemic virus-mediated inflammation and injury within the graft itself are required.ConclusionsThese data suggest that in this mouse model, the predominant mechanism of allograft injury in PyV-associated injury is due to an augmented alloimmune T cell response driven by virus-induced inflammation/injury within the graft. These studies highlight the important interplay between viral infection and alloimmunity in a model system.

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“…Three studies have used the mouse kidney transplant model to investigate the effect of transplant‐associated viral infections . In mice infected with polyomavirus the allograft developed worse histological injury with increased numbers of CD8+ T cells compared with virus‐free recipients .…”

Section: Resultsmentioning

confidence: 99%

Systematic review of mouse kidney transplantation

2013

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A mouse model of kidney transplantation was first described in 1973 by Skoskiewicz et al. Although the mouse model is technically difficult, it is attractive for several reasons: the mouse genome has been characterized and in many aspects is similar to man and there is a greater diversity of experimental reagents and techniques available for mouse studies than other experimental models. We reviewed the literature on all studies of mouse kidney transplantation to report the donor and recipient strain combinations that have been investigated and the resultant survival and histological outcomes. Some models of kidney transplantation have used the transplanted kidney as a life-supporting organ, however, in many studies the recipient mouse's native kidney has been left in situ. Several different combinations of inbred mouse strains have been reported, with varying degrees of injury, survival or tolerance because of haplotype differences. This model has been exceptionally useful as an investigational tool to understand multiple aspects of transplantation including acute rejection, cellular and humoral rejection mechanisms and their treatment. Furthermore, this model has been used to investigate disease mechanisms beyond transplant rejection including intrinsic renal disease and infection-associated pathology.

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Adaptive Immunity Rather Than Viral Cytopathology Mediates Polyomavirus-Associated Nephropathy in Mice

Cited by 12 publications

References 47 publications

Microbes and Allogeneic Transplantation

Microbes and Allogeneic Transplantation

Alloimmunity But Not Viral Immunity Promotes Allograft Loss in a Mouse Model of Polyomavirus-Associated Allograft Injury

Systematic review of mouse kidney transplantation

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