Prolonged Graft Survival in Older Recipient Mice Is Determined by Impaired Effector T-Cell but Intact Regulatory T-Cell Responses

Elderly organ transplant recipients represent a fast growing segment of patients on the waiting list. We examined age-dependent CD4+ T-cell functions in a wild-type (WT) and a transgenic mouse transplant model and analyzed the suppressive function of old regulatory T-cells. We found that splenocytes of naïve old B6 mice contained significantly higher frequencies of T-cells with an effector/memory phenotype (CD4+CD44highCD62Llow). However, in-vitro proliferation (MLR) and IFNγ-production (ELISPOT) were markedly reduced with increasing age. Likewise, skin graft rejection was significantly delayed in older recipients and fewer graft infiltrating CD4+T-cells were observed. Old CD4+ T-cells demonstrated a significant impaired responsiveness as indicated by diminished proliferation and activation. In contrast, old alloantigen-specific CD4+CD25+FoxP3+ T-cells demonstrated a dose-dependent well-preserved suppressor function. Next, we examined characteristics of 18-month old alloreactive T-cells in a transgenic adoptive transfer model. Adoptively transferred old T-cells proliferated significantly less in response to antigen. Skin graft rejection was significantly delayed in older recipients, and graft infiltrating cells were reduced. In summary, advanced recipient age was associated with delayed acute rejection and impaired CD4+ T-cell function and proliferation while CD4+CD25+FoxP3+ T-cells (Tregs) showed a well-preserved function

The unmasking of Pneumocystis jiroveci pneumonia during reversal of immunosuppression: Case reports and literature review

Background: Pneumocystis jiroveci pneumonia (PCP) is an important opportunistic infection among immunosuppressed patients, especially in those infected with human immunodeficiency virus (HIV). The clinical presentation of PCP in immunosuppressed patients have been well-reported in the literature. However, the clinical importance of PCP manifesting in the setting of an immunorestitution disease (IRD), defined as an acute symptomatic or paradoxical deterioration of a (presumably) preexisting infection, which is temporally related to the recovery of the immune system and is due to immunopathological damage associated with the reversal of immunosuppressive processes, has received relatively little attention until recently. Case presentation: We aim to better define this unique clinical syndrome by reporting two cases of PCP manifesting acutely with respiratory failure during reversal of immunosuppression in non-HIV infected patients, and reviewed the relevant literature. We searched our databases for PCP cases manifesting in the context of IRD according to our predefined case definition, and reviewed the case notes retrospectively. A comprehensive search was performed using the Medline database of the National Library of Medicine for similar cases reported previously in the English literature in October 2003. A total of 28 non-HIV (excluding our present case) and 13 HIV-positive patients with PCP manifesting as immunorestitution disease (IRD) have been reported previously in the literature. During immunorestitution, a consistent rise in the median CD4 lymphocyte count (28/μL to 125/μL), with a concomitant fall in the median HIV viral load (5.5 log10 copies/ml to 3.1 log10 copies/ml) was observed in HIV-positive patients who developed PCP. A similar upsurge in peripheral lymphocyte count was observed in our patients preceding the development of PCP, as well as in other non-HIV immunosuppressed patients reported in the literature. Conclusions: PCP manifesting as IRD may be more common than is generally appreciated. Serial monitoring of total lymphocyte or CD4 count could serve as a useful adjunct to facilitate the early diagnosis and pre-emptive treatment of this condition in a wide range of immunosuppressed hosts, especially in the presence of new pulmonary symptoms and/or radiographic abnormalities compatible with the diagnosis. © 2004 Wu et al; licensee BioMed Central Ltd.published_or_final_versio

Kidney transplant in diabetic patients: modalities, indications and results

<p>Abstract</p> <p>Background</p> <p>Diabetes is a disease of increasing worldwide prevalence and is the main cause of chronic renal failure. Type 1 diabetic patients with chronic renal failure have the following therapy options: kidney transplant from a living donor, pancreas after kidney transplant, simultaneous pancreas-kidney transplant, or awaiting a deceased donor kidney transplant. For type 2 diabetic patients, only kidney transplant from deceased or living donors are recommended. Patient survival after kidney transplant has been improving for all age ranges in comparison to the dialysis therapy. The main causes of mortality after transplant are cardiovascular and cerebrovascular events, infections and neoplasias. Five-year patient survival for type 2 diabetic patients is lower than the non-diabetics' because they are older and have higher body mass index on the occasion of the transplant and both pre- and posttransplant cardiovascular diseases prevalences. The increased postransplant cardiovascular mortality in these patients is attributed to the presence of well-known risk factors, such as insulin resistance, higher triglycerides values, lower HDL-cholesterol values, abnormalities in fibrinolysis and coagulation and endothelial dysfunction. In type 1 diabetic patients, simultaneous pancreas-kidney transplant is associated with lower prevalence of vascular diseases, including acute myocardial infarction, stroke and amputation in comparison to isolated kidney transplant and dialysis therapy.</p> <p>Conclusion</p> <p>Type 1 and 2 diabetic patients present higher survival rates after transplant in comparison to the dialysis therapy, although the prevalence of cardiovascular events and infectious complications remain higher than in the general population.</p

Outcome after renal transplantation in a "senior" program: the croatian experience

BACKGROUND: The Eurotransplant "senior" program allocates kidneys from elderly donors to patients >65 years old. It aims to increase the number of renal transplantations. Kidneys are allocated locally without human leukocyte antigen (HLA) matching to decrease the cold ischemia time. Croatia has introduced its own "senior" program based on HLA matching. We compared results with those from Eurotransplant. ----- METHODS: We identified and prospectively followed all patients aged of >/=65 years who underwent a first renal transplantation. We recorded their HLA matching, cold ischemia time, renal function, surgical and medical complications, and duration of hospitalization. ----- RESULTS: Through October 2007, 22 elderly patients received an allograft from donors who were >65 years old. There were 8 female and 14 male patients of mean age at transplantation of 67.4 years. Mean donor age was 66 years. The number of HLA mismatches ranged from 1 to 5, and cold ischemia time from 7 to 15 hours. One-year patient survival was 95.4%, and graft survival was 81.8%. Delayed graft function, defined as the need for dialysis for >7 days after transplantation, occurred in 63.6% of patients. Older recipients required prolonged hospitalization after transplantation (45 days; range, 16-131). Frequent posttransplant complications included posttransplant diabetes mellitus in 1 patient, delayed wound healing in 5 patients, and lymphocoel in 2 patients. Maligancies occurred in 3 patients, neoplasm of the native kidney, posttransplant lymphoproliferative disease, and skin cancer. One patient experienced acute rejection that was successfully treated with steroids. Seventeen patients experienced 20 viral infections. There was only 1 serious infection (pulmonary tuberculosis). The major problems were cardiovascular complications which occurred in 40.9% of patients. ----- CONCLUSION: Renal transplantation in elderly patients is associated with increased incidence of posttransplant surgical and medical complications which demand prolonged hospitalization. Incidence of acute rejections in elderly patients is significantly decreased with HLA matching, without prolongation of the cold ischemia time. Good results justify renal transplantation in this group of patients