Reactivation of Latent Rat Cytomegalovirus by a Combination of Immunosuppression and Administration of Allogeneic Immunocompetent Cells

Jh, Bruning; Bruggeman, C. A.; Boven, van M.; Pj, van Breda Vriesman

doi:10.1097/00007890-198905000-00040

Cited by 14 publications

(4 citation statements)

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“…In another model, Olding et al [120] found that MCMV could be activated from apparently uninfected murine spleen cells by cocultivation with allogenic, but not syngeneic, fibroblasts. These observations were recently confirmed by Bruning et al in studies in the rat [23]. Therefore, allogenic stimulation by the graft might also play a role in the occurrence of CMV infection after allograft rejection in humans.…”

Section: Relationship Between Cytomegalovirus and Rejectionsupporting

confidence: 59%

Cytomegalovirus infection after organ transplantation: an update with special emphasis on renal transplantation

Son

The²

1989

Transplant Int

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Cytomegalovirus infections are still the most important infectious complications after organ transplantation. Besides historical notes this review will deal with new aspects concerning the epidemiology of the CMV, diagnostic modalities of CMV infection, the delicate counterbalance between the immune system and the CMV, as well as the symptomatology of this infection. Furthermore, aspects like prophylaxis and new, promising therapeutic regimes for treatment of infection will be dealt with. Although this update is applicable for all types of solid organ transplantation, emphasis will be on renal transplantation.

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Section: Relationship Between Cytomegalovirus and Rejectionsupporting

confidence: 59%

Cytomegalovirus infection after organ transplantation: an update with special emphasis on renal transplantation

Son

The²

1989

Transplant Int

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“…In addition to cytokines, other possible causes of reactivation of latent CMV with this sepsis model could include antigenic stimulation, shock, elevated catecholamines, or localized pulmonary inflammation. Allogeneic stimulation is known to reactivate CMV [31,47,48], and bacterial antigens introduced by CLP may have provided this type of stimulation. Similarly, elevated catecholamine levels, which may have been precipitated in this model by shock after CLP, have recently been shown to stimulate HCMV reactivation [49].…”

Section: Discussionmentioning

confidence: 99%

Intra‐abdominal Bacterial Infection Reactivates Latent Pulmonary Cytomegalovirus in Immunocompetent Mice

et al. 2002

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Critically ill surgery patients are susceptible to pulmonary reactivation of latent cytomegalovirus (CMV), but what triggers this reactivation is unknown. Immunosuppression and bacterial sepsis are thought to stimulate reactivation of CMV, and in this study it was hypothesized that immunosuppressive effects of surgery with or without concomitant bacterial infection may reactivate latent CMV. Mice infected with CMV were allowed to develop latent infections. Latently infected mice underwent a laparotomy with cecal ligation and puncture (CLP; n=30), a laparotomy alone (sham; n=10), or no surgery (control; n=5). Lung tissue homogenates were evaluated for viral activity, and, 2 and 3 weeks after CLP, lungs of 7 of 7 and 5 of 5 mice, respectively, showed reactivation of latent CMV. In contrast, lungs from all sham-operated animals and controls showed no viral reactivation. These findings demonstrate that surgery with subsequent intra-abdominal bacterial infection reactivated CMV in lungs of latently infected mice. The mechanism of this reactivation is unknown but likely involves cytokines induced by sepsis.

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“…31 Rejection has also been shown to induce CMV reactivation in a rat model of kidney transplantation. 32 Thus the interrelationship of CMV infection and rejection is complex and probably acts in both directions.…”

Section: Discussionmentioning

confidence: 99%

Cytomegalovirus infection is associated with increased inflammation and severe bile duct damage in rat liver allografts

et al. 1998

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It has been suggested that cytomegalovirus (CMV) infection is involved in allograft rejection. In liver transplantation, it has been suggested that CMV is associated with the development of vanishing bile duct syndrome (VBDS), and persistent CMV has been found in liver grafts that develop chronic rejection. In this experimental study, the effect of rat CMV (RCMV) infection on intragraft changes was investigated in a rat model of acute liver allograft rejection. Liver transplantations were performed in a rat strain combination of PVG (RT1 c ) = BN (RT1 n ). No immunosuppression was given. One group of animals was infected with RCMV Maastricht Strain (10 5 plaque-forming units, intraperitoneally), and another group was left uninfected. The grafts were examined histologically after the rats were killed on postoperative days 7 through 9 at the early phase and days 20 through 30 at the late phase of rejection. Immunohistochemical studies were performed to demonstrate the immunological activation markers major histocompatibility complex class II and interleukin 2 receptors, intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1), and their ligands. RCMV infection was demonstrated from the grafts by culture and direct antigen detection. In liver allografts undergoing acute rejection, CMV significantly increased portal inflammation and caused more severe bile duct damage than in the uninfected grafts. CMV was also linked to the induction of VCAM-1 in the endothelial cells. The ongoing infection was found to vary over time in the different structures of the liver grafts, including the vascular endothelium and bile ducts. Our results support an association between CMV infection and the immunological mechanisms of rejection, as well as the role of CMV in the development of bile duct damage in liver allografts. (HEPATOLOGY 1998;27;996-1002.)Cytomegalovirus (CMV) infection is a major source of morbidity and mortality in transplant recipients and other immunocompromised patients. The incidence of CMV infection among liver transplant recipients is high, and 40% to 70% of these patients develop a symptomatic CMV disease. 1-4 A variety of clinical manifestations of CMV infection, such as fever, pneumonitis, gastroenteritis, and hepatitis, have been described. The liver is a privileged site for CMV, and the liver graft has been found to be the most commonly affected organ in primary CMV infections. 1 CMV has also been suggested to be linked to organ allograft rejection in both kidney and heart transplantation. [5][6][7] In liver transplantation, the importance of concomitant CMV infection during late acute rejections has been reported. 8 An association between CMV and vanishing bile duct syndrome (VBDS) in hepatic allografts has been found, 9 and persistence of CMV DNA in hepatocytes, 10,11 bile ducts, and vascular structures 11 of the liver has been demonstrated in patients with VBDS. We recently showed that persistent CMV infection in liver allografts is associated with chronic rejection. 11 Va...

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Reactivation of Latent Rat Cytomegalovirus by a Combination of Immunosuppression and Administration of Allogeneic Immunocompetent Cells

Cited by 14 publications

References 0 publications

Cytomegalovirus infection after organ transplantation: an update with special emphasis on renal transplantation

Cytomegalovirus infection after organ transplantation: an update with special emphasis on renal transplantation

Intra‐abdominal Bacterial Infection Reactivates Latent Pulmonary Cytomegalovirus in Immunocompetent Mice

Cytomegalovirus infection is associated with increased inflammation and severe bile duct damage in rat liver allografts

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