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• W4382055950 abstract "Introduction: Recipient age has a substantial impact on alloimmunity and outcomes after organ transplantation. Increased rates of infections, malignancies, mortalities, and a more challenging treatment of acute rejections are characteristic and related to synergistic effects of immune senescence and immunosuppression. Effects of aging on Intestinal Transplantation (ITx) are poorly understood. Aim: To delineate the effects of aging on alloimmunity and transplant survival in an experimental model of ITx. Materials and Methods: Intestinal allografts from young (2 months) Sprague-Dawley rats were transplanted into either young or old Wistar rats (2 or >9 months, respectively, n=7/group). Intestinal graft and blood samples were collected at 30 minutes, 5, 7, 9 post-operative days (POD) and at the clinical endpoint time, determined by clinical score. Recipient survival, histopathological analysis assessing acute cellular rejections (ACR) based on the Wu Score, intestinal absorptive capacity, kinetics of CD4 and CD8 frequencies (flow cytometry) were collected. Donor specific allorecognition responses using splenocytes of old and young recipient rats were evaluated by Mixed Lymphocyte Reaction (MLR) assays. Results: Intestinal graft analysis performed by 6-8 POD demonstrated comparable number of acute rejection episodes, but with different degree of severity (Figure 1). Furthermore, glycemia curves were similar in both groups, demonstrating comparable graft absorptive capacity. Prior to transplantation, old rats exhibited a reduced number of CD4+ T-cells systemically. After ITx, kinetics of CD4+ and CD8+ frequency in blood and gut tissue was similar in both groups. Allo-specific response of CD4 and CD8 cells after allogenic antigen stimulation by MLR assay demonstrated age-independent proliferation rates. Despite of the difference of rejection severity rate between groups, the survival of old recipient was prolonged (11.8 ± 1.6 vs 8.3 ± 0.2 POD in old vs. young recipients, Figure 2), this was determined by less severe clinical score mainly due to a reduced amount of body weight loss (OR: 20% vs YR: 25%). Conclusion: The preliminary results of using OR for intestinal grafts showed an increase severity of the rejection episodes observed, but with lower impact in clinical score. This experimental study is of translational relevance supporting the concept of transplanting older recipients in need of intestinal transplants. It is to highlight the need to further using the model with standard immunosuppression, to understand the response to therapy, and the immunobiology related to aging.Figure 1.: Severity grade of ACR in OR and YR according to Wu ScoreFigure 2.: Survival curves defined by Clinical Score" @default.
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• W4382055950 date "2023-06-27" @default.
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• W4382055950 title "123: First intestinal transplant model in rats to assess the impact of aging on cellular rejection kinetics, clinical manifestation, and survival." @default.
• W4382055950 doi "https://doi.org/10.1097/01.tp.0000945948.71486.da" @default.
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