Serum hypoalbuminemia predicts late mortality on the liver transplant waiting list.
Transplantation 99(1):158 (2015)
The reduction of liver transplant wait list mortality remains a priority for transplant programs and depends on the accurate stratification of patients by mortality risk. Although estimation of 90-day mortality by Model for End-Stage Liver Disease (MELD) score has improved wait list survival, it...
Regulatory T cells occupy an isolated niche in the intestine that is antigen independent.
Cell Reports 9(5):1567 (2014)
Regulatory T cells (Tregs) are CD4(+) T cells that maintain immune homeostasis and prevent autoimmunity. Like all CD4(+) T cells, Tregs require antigen-specific signals via T cell receptor-major histocompatibility complex class II (TCR-MHCII) interactions for their development. However, the requ...
Immunosuppression: trends and tolerance?
Clinics in Liver Disease 18(3):687 (2014)
Advances in pharmacologic immunosuppression are responsible for the excellent outcomes experienced by recipients of liver transplants. However, long-term follow-up of these patients reveals an increasing burden of morbidity and mortality that is attributable to these drugs. The authors summarize...
Donor assessment scores: relevance and complete irrelevance.
Liver Transplantation and Surgery 18 Suppl 2:S25 (2012)
1. Donor assessment scores can be used to prognosticate recipient outcomes but are often not clinically relevant. 2. The donor risk index, the survival outcomes following liver transplantation score, and the Donor Model for End-Stage Liver Disease score have specific advantages and disadvantages...
Innate immunity in transplant tolerance and rejection.
Immunological Reviews 241(1):39 (2011)
Historically, research on transplant rejection and tolerance has focused on cells of the adaptive immune system, especially T cells. Anti-graft effector T cells are necessary and sufficient for the rejection of most allografts, while regulatory T cells, either arising naturally or as a result of...
Late surgical complications following liver transplantation.
Liver Transplantation and Surgery 15 Suppl 2:S12 (2009)
1. Biliary strictures and incisional hernias are the most common surgical complications encountered late after liver transplantation. 2. Anastomotic biliary strictures are amenable to endoscopic intervention and rarely need surgical intervention. 3. The presence of a biliary stricture mandates a...
Kidney transplantation at the University of Pennsylvania: 1998-2008.
Clinical transplants :143 (2009)
Kidney transplantation at the University of Pennsylvania has grown substantially over the past 11 years. Although our transplant volume has increased primarily as a consequence of multiorgan transplants as well as the utilization of historically "marginal" allografts, our post-transplantation ou...
Migratory and lymphoid-resident dendritic cells cooperate to efficiently prime naive CD4 T cells.
Immunity 29(5):795 (2008)
To initiate an adaptive immune response, rare antigen-specific naive CD4(+) T cells must interact with equally rare dendritic cells (DCs) bearing cognate peptide-major histocompatibility complex (MHC) complexes. Lymph nodes (LNs) draining the site of antigen entry are populated by lymphoid-resid...
Mechanisms underlying blockade of allograft acceptance by TLR ligands.
Journal of Immunology 181(3):1692 (2008)
Immune activation via TLRs is known to prevent transplantation tolerance in multiple animal models. To investigate the mechanisms underlying this barrier to tolerance induction, we used complementary murine models of skin and cardiac transplantation in which prolonged allograft acceptance is eit...
A direct comparison of rejection by CD8 and CD4 T cells in a transgenic model of allotransplantation.
Archivum Immunologiae et Therapiae Experimentalis 56(3):193 (2008)
The relative contributions of CD4+ and CD8+ T cells to transplant rejection remain unknown. The authors integrated a previous model of CD4-mediated graft rejection with a complementary model of CD8-mediated rejection to directly compare the function of graft-reactive CD4+ and CD8+ lymphocytes in...
Interleukins 27 and 6 induce STAT3-mediated T cell production of interleukin 10.
Nature Immunology 8(12):1363 (2007)
Interleukin 10 (IL-10) has a prominent function in regulating the balance between protective and pathological T cell responses. Consistent with that activity, many sources of this cytokine are found in vivo, including from myeloid cells and a variety of T cell subsets. However, although there ar...
Deacetylase inhibition promotes the generation and function of regulatory T cells.
Nature Medicine 13(11):1299 (2007)
Histone/protein deacetylases (HDACs) regulate chromatin remodeling and gene expression as well as the functions of more than 50 transcription factors and nonhistone proteins. We found that administration of an HDAC inhibitor (HDACi) in vivo increased Foxp3 gene expression, as well as the product...
Availability of suitable islet donors in the United States.
Transplantation 84(2):280 (2007)
We characterize donor utilization for islet transplantation and estimate the number of recipients who could achieve normoglycemia through islet transplantation if the current donor pool were used.
Potential islet donors from all United Network for Organ Sharing donors (1/00-5/04) were identified...
Cutting edge: T cell requirement for CD28 costimulation is due to negative regulation of TCR signals by PTEN.
Journal of Immunology 177(7):4262 (2006)
Recent studies suggest that the phosphatase and tensin homolog deleted on chromosome 10 (PTEN) plays a critical role in the maintenance of self-tolerance. Using T cell-specific PTEN knockout mice (PTENDeltaT), we have identified a novel mechanism by which PTEN regulates T cell tolerance. We foun...
T-reg mediated suppression of the allograft response in the draining lymph node.
Transplantation 81(7):1063 (2006)
We previously demonstrated that T-regs inhibit proliferation of graft-reactive T cells in the draining lymph node (DLN), suggesting that this site may be important for regulation. TCR transgenic mice (TS1) specific for viral hemagglutinin (HA) provided antigen-specific T cells for adoptive trans...
Lack of benefit of pre-transplant locoregional hepatic therapy for hepatocellular cancer in the current MELD era.
Liver Transplantation 12(4):665 (2006)
The potential for disease progression in patients awaiting liver transplantation for hepatocellular carcinoma (HCC) has encouraged many centers to employ pre-transplant radiofrequency ablation or chemoembolization in an attempt to control tumor burden while patients are on the wait list. Despite...
Combined orthotopic heart and liver transplantation: the need for exception status listing.
Liver Transplantation 10(12):1539 (2004)
Through May 2004, 33 combined orthotopic heart-liver transplants (OHT/OLT) have been performed nationwide. No published data exist to date regarding outcomes of patients awaiting such transplants, although progression of two organ disease processes may contribute to premature death for waiting p...