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BALB/c Recipients (c + recipient)
Selected AbstractsGraft rejection mediated by CD4+ T cells via indirect recognition of alloantigen is associated with a dominant Th2 responseEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 3 2005Keri Csencsits Abstract CD4+ T cells that respond to indirectly presented alloantigen have been shown to mediate chronic rejection, however, the role of the indirect pathway in acute rejection has yet to be completely elucidated. To this end, BALB/c or C57BL/6 mice were depleted of CD8+ T cells and transplanted with class II transactivator (CIITA)-deficient cardiac allografts, which cannot directly present class II alloantigens to CD4+ T cells. In this manner, the rejection response by CD4+ cells was forced to rely upon the indirect recognition pathway. When not depleted of CD8+ cells, both BALB/c and C57BL/6 mice rejected CIITA,/, allografts and a polarized Th1 response was observed. In contrast, when BALB/c recipients of CIITA,/, allografts were depleted of CD8+ T cells, the grafts were acutely rejected and a strong Th2 response characterized by eosinophil influx into the graft was observed. Interestingly, CD8-depleted C57BL/6 recipients of CIITA,/, allografts did not acutely reject their transplants and a Th2 response was not mounted. These findings indicate that CD4+ T cells responding to indirectly presented alloantigens mediate graft rejection in a Th2-dominant manner, and provide further evidence for the role of Th2 responses in acute graft rejection. [source] Infusion of Mesenchymal Stem Cells and Rapamycin Synergize to Attenuate Alloimmune Responses and Promote Cardiac Allograft ToleranceAMERICAN JOURNAL OF TRANSPLANTATION, Issue 8 2009W. Ge The inherent immunosuppressive properties and low immunogenicity of mesenchymal stems cells (MSCs) suggested their therapeutic potential in transplantation. We investigated whether MSCs could prolong allograft survival. Treatment involving infusion of MSCs into BALB/c recipients 24 hours after receiving a heart allograft from a C57BL/6 donor significantly abated rejection and doubled graft mean survival time compared to untreated recipients. Furthermore, combination therapy of MSCs and low-dose Rapamycin (Rapa) achieved long-term heart graft survival (>100 days) with normal histology. The treated recipients readily accepted donor skin grafts but rejected third-party skin grafts, indicating the establishment of tolerance. Tolerant recipients exhibited neither intragraft nor circulating antidonor antibodies, but demonstrated significantly high frequencies of both tolerogenic dendritic cells (Tol-DCs) and CD4+CD25+Foxp3+T cells in the spleens. Infusion of GFP+C57BL/6-MSCs in combination with Rapa revealed that the GFP-MSCs accumulated in the lymphoid organs and grafts of tolerant recipients. Thus, engraftment of infused MSCs within the recipient's lymphoid organs and allograft appeared to be instrumental in the induction of allograft-specific tolerance when administered in combination with a subtherapeutic dose of Rapamycin. This study supports the clinical applicability of MSCs in transplantation. [source] Living Donor and Split-Liver Transplants in Hepatitis C Recipients: Does Liver Regeneration Increase the Risk for Recurrence?AMERICAN JOURNAL OF TRANSPLANTATION, Issue 2 2005Abhinav Humar Concern exists that partial liver transplants (either a living donor [LD] or deceased donor [DD] in hepatitis C virus (HCV)-positive recipients may be associated with an increased risk for recurrence. From 1999 to 2003, at our institution, 51 HCV-positive recipients underwent liver transplants: 32 whole-liver (WL) transplants, 12 LD transplants and 7 DD split transplants. Donor characteristics differed in that WL donors were older, and LD livers had lower ischemic times. Recipient characteristics were similar except that mean MELD scores in LD recipients were lower (p < 0.05). With a mean follow-up of 28.3 months, 46 (90%) recipients are alive: three died from HCV recurrent liver disease and two from tumor recurrence. Based on 1-year protocol biopsies, the incidence of histologic recurrence in the three groups is as follows: WL, 81%; LD, 50% and DD split, 86% (p = 0.06 for LD versus WL). The mean grade of inflammation on the biopsy specimens was: WL, 1.31; LD, 0.33 and DD split, 1.2 (p = 0.002 for LD versus WL; p = 0.03 for LD versus DD split). Mean stage of fibrosis was: WL, 0.96; LD, 0.22 and DD split, 0.60 (p = 0.07 for LD versus WL). Liver regeneration does not seem to affect hepatitis C recurrence as much, perhaps, as factors such as DD status, donor age and cold ischemic time. [source] The Impact of Preexisting or Acquired Kaposi Sarcoma Herpesvirus Infection in Kidney Transplant Recipients on Morbidity and SurvivalAMERICAN JOURNAL OF TRANSPLANTATION, Issue 11 2009C. Francès The impact of preexisting or acquired Kaposi sarcoma herpesvirus (KSHV) infection in kidney transplant recipients was evaluated in a prospective study. Serum collected from kidney donors and recipients before transplantation were tested for antibodies against KSHV latent nuclear antigen. Three groups of recipients were defined: group A (KSHV+), group B (KSHV,, KSHV+ donor) and group C (donor and recipient KSHV,). Blood was collected from recipients, every 3 months for 3 years, for KSHV viremia (groups A and B), quantitative (group A) and qualitative serology (group B). Data of group C recipients were extracted from a French database. The prevalence of KSHV antibodies was 1.1% in donors and 3.2% in recipients. There were respectively 161, 64 and 4744 recipients in groups A, B and C. In group A, 13% developed Kaposi's sarcoma (KS). Age >53.5 years (p = 0.025) and black skin (p = 0.0054) were associated with KS development. In group B, three recipients developed clinical manifestations related to KSHV infection. There was no difference in terms of survival and graft loss between the three groups. In conclusion, although kidney recipients should be aware of the additional risk of KSHV morbidity, KSHV+ recipients should not be systematically excluded from kidney transplantation. [source] L/I-7 Comparison of HCV outcomes in recipients of expanded-criteria, living donor, and standard liver graftsCLINICAL TRANSPLANTATION, Issue 2006M. Kinkhabwala Introduction:, Living donor (LD) and expanded-criteria donor (ECD) livers are important sources of organ transplants in some regions. Hepatitis C virus (HCV) remains the most common reason for end-stage liver disease in the United States. It is unclear whether ECD and LD grafts are associated with poorer outcomes in hepatitis C recipients, as compared with non-ECD (standard [STD]) MELD-allocated livers. The aim of this retrospective study was to compare long-term hepatitis C recurrence rates and outcomes in recipients of ECD, LD, and STD grafts. Methods:, The cohort of patients analyzed comprised all adult hepatitis C transplant recipients between 1/1/01 and 11/1/04 (minimum follow-up, 1 year). Recipients not surviving the immediate perioperative period (90 days) were excluded. Censored events were defined by disease-free graft survival. Disease recurrence was defined by histologically confirmed hepatitis C and at least stage II fibrosis. ECDs were identified according to accepted criteria (e.g., age, steatosis, ischemia, donation after cardiac death, abnormal biopsy). Results:, In all, 120 patients formed the study cohort, with 79 ECD, 27 LD, and 14 STD grafts. The mean recipient MELD was 19.8 overall (range, 6 to 43), 20.1 (ECD), 14.1 (LD), and 24.7 (STD). The mean time to censored event was 709 days overall, 631 (ECD), 884 (STD), and 846 (LD). The 2-year disease-free survival rate was 44% (ECD), 55.6% (LD), and 70.7% (STD), by Kaplan-Meier analysis. Comparison of the curves indicated a significant difference between ECD and STD recipients, but no difference between ECD and LD recipients. Conclusions:, Recipients with hepatitis C who received ECD grafts had poorer outcomes in our experience, as compared with those receiving STD grafts. LD grafts, which can be viewed as a subset of ECD grafts, also had poorer outcomes than STD whole grafts, but this difference was not statistically significant. [source] | ||||||||||