Donor-specific cellular immune response against human cardiac valve allografts

Hoekstra, Franciska; Knoop, C. J.; Vaessen, L. M. B.; Wassenaar, Claas; Jutte, N. H. P. M.; Bos, Egbert; Bogers, Ad J.J.C.; Weimar, Willem

doi:10.1016/s0022-5223(96)70250-7

Cited by 58 publications

(41 citation statements)

References 14 publications

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“…In addition to the humoral response, Hoekstra and associates have demonstrated a cellmediated immune reaction to cryopreserved homografts. T cells have been directly implicated in the inflammatory process that is associated with early and late allograft valve failure [6,7]. An important advantage of Contegra is storage in dilute, buffered glutaraldehyde, which retains leaflet-and conduit-wall compliance.…”

Section: Discussionmentioning

confidence: 99%

Comparison of bovine jugular vein with pulmonary homograft conduits in children less than 2 years of age☆

Fiore¹,

Ruzmetov²,

Huynh³

et al. 2010

European Journal of Cardio-Thoracic Surgery

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Section: Discussionmentioning

confidence: 99%

Comparison of bovine jugular vein with pulmonary homograft conduits in children less than 2 years of age☆

Fiore¹,

Ruzmetov²,

Huynh³

et al. 2010

European Journal of Cardio-Thoracic Surgery

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“…These findings are in agreement with previous reports of donor-specific immune responses generated after allograft implantation in animal models and in humans. 13,14,20,21 Taken together, there appears to be 2 important processes that may predispose cryopreserved valve grafts to structural failure. First, there is an early infiltration with myeloid cells regardless of allostimulation.…”

Section: Valve Grafts 7 Days After Implantationmentioning

confidence: 99%

Cryopreservation of Rat Aortic Valves Results in Increased Structural Failure

Légaré

Lee²

2000

Circulation

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Background-The cause of valve allograft failure is most likely multifactorial and may include mechanical, immunological, and other factors. Cryopreservation of these valves is often used to extend storage times. However, there has been considerable confusion as to the effects of cryopreservation on valve durability. Our objective was to determine the effects of cryopreservation on histopathological changes in rat aortic valve grafts. Methods and Results-Syngeneic rat aortic valve grafts (Lewis to Lewis; nϭ24) and allogeneic rat aortic valve grafts (Brown Norway to Lewis; nϭ24) were implanted infrarenally, either fresh or after cryopreservation. At 7, 14, and 28 days, the valves were explanted, and histological and immunohistochemical examinations were performed in a blinded fashion. Fresh syngeneic graft leaflets retained their normal structure for the 28-day period of observation. Cryopreserved syngeneic grafts showed retrovalvar thrombus formation, with leaflet destruction at 7, 14, and 28 days. Fresh allogeneic graft leaflets showed significant leaflet thickening and progressive destruction at 14 and 28 days. Cryopreserved allogeneic grafts had evidence of retrovalvar thrombus formation with leaflet destruction at 7, 14, and 28 days. Cryopreserved syngeneic grafts resulted in significant infiltration of mononuclear (ED1 ϩ ) cells not seen with fresh syngeneic grafts but similar to fresh allogeneic grafts. All allogeneic grafts resulted in significant infiltration of T-lymphocytes (CD3 ϩ , CD8 ϩ , CD43 ϩ ). Conclusions-Cryopreservation appears to predispose syngeneic and allogeneic rat aortic valve leaflets to accelerated injury and destruction.

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“…Others reported identical in®ltration of in¯ammatory cells in cryopreserved pulmonary valve allograft explants, while the aortic valve explants were free from any cellular component [3]. Finally, Hoekstra et al demonstrated donor-speci®c cytotoxicity of in®ltrating lymphocytes found in explanted AVC [21]. Also, reviewing these studies, severe structural failure associated with in®ltration of immune competent cells is more frequently seen in pediatric patients, in whom pulmonary AVC s are predominantly implanted right-sided.…”

Section: Discussionmentioning

confidence: 98%

Circulating donor-specific cytotoxic T lymphocytes with high avidity for donor human leukocyte antigens in pediatric and adult cardiac allograft valved conduit recipients✩

Oei

Welters

Knoop

et al. 2000

European Journal of Cardio-Thoracic Surgery

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Objective: Speci®c immunological responses may be involved in the process of cryopreserved allograft valved conduit (AVC) degeneration, which is more frequently seen in young recipients. Rejection of heart and corneal allografts is preceded by an increase in the fraction of cytotoxic T lymphocytes (CTL) with high avidity for donor human leukocyte antigens (HLA) circulating in both peripheral blood and the affected graft. These donor-speci®c high-avidity CTLs are regarded as the destructive cells capable of causing graft damage. To monitor the precursors of these cells (CTLp) in young and adult AVC recipients, in vitro quantitative tests were performed on sequentially taken blood samples to quantitate CTLp frequencies and their avidity for donor antigens. Method: Six children and nine adults who received a cryopreserved AVC in the period between 1994 and 1997 were included in the study. From these patients, two to six blood samples were obtained up to 3 years after valve implantation. The number of circulating CTLp present within the peripheral blood mononuclear cell (PBMC) population was determined by limiting dilution analysis (LDA). The fraction of CTLp with high avidity for donor HLA class I was determined by addition of CD8 monoclonal antibodies (mAb) during the cytotoxic phase of the assay. Third-party stimulator cells were used to verify the donor-speci®city of the response. Results: The number of donor-speci®c CTLp increased signi®cantly in the period 6±12 months after AVC implantation, while third-party-speci®c CTLp frequencies were not affected. Additionally, we found a signi®cant increase of the high-avidity fraction of CTLp directed against donor antigens as early as during the ®rst 6 months after AVC implantation. The fraction of high-avidity CTLp remained signi®cantly higher post-compared with pre-implantation, even after 12 months. We observed no signi®cant difference in the kinetics of CTLp frequencies between pediatric and adult AVC recipients. Conclusion: Implantation of cryopreserved human AVC induces an increase in the total number of circulating CTLp directed against donor HLA class I in both adults and children. The shift towards more destructive high-avidity CTLp in the peripheral blood indicates their potential damaging effect towards the heart valve allograft. q

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Donor-specific cellular immune response against human cardiac valve allografts

Cited by 58 publications

References 14 publications

Comparison of bovine jugular vein with pulmonary homograft conduits in children less than 2 years of age☆

Comparison of bovine jugular vein with pulmonary homograft conduits in children less than 2 years of age☆

Cryopreservation of Rat Aortic Valves Results in Increased Structural Failure

Circulating donor-specific cytotoxic T lymphocytes with high avidity for donor human leukocyte antigens in pediatric and adult cardiac allograft valved conduit recipients✩

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