INTRODUCTION: Right lobe donor hepatectomy (RLDH) is a potential source of liver allografts given the ongoing shortage of deceased donor organs available. Since there is no live donor registry in the United States, a population-based, unsolicited state-wide analysis has yet to be reported. METHODS: The New York (NY) State Inpatient Database was used to query 1,524 elective liver lobectomies performed from 2001 to 2006. RLDH were identified in this cohort (n = 195; 13%). Most common indications for elective right lobe hepatectomy (ERH) were metastatic colon cancer (50%) and hepatocellular carcinoma (HCC) (34%). Primary outcomes were mortality, perioperative resources and major postoperative complications. RESULTS: After a dramatic drop in 2002, there was a slow increase in RLDH from 2003 to 2006 in New York. Donors were younger (median age 36 vs. 60 years, P < 0.0001) and healthier (75% with no comorbidities vs. 18%, P < 0.0001) than patients undergoing ERH for other causes. Median length of hospital stay was 7 days in both groups. Donors were less likely to require blood transfusion (22.6 vs. 62.8%, P < 0.0001) and received less blood (mean 0.10 units vs. 2.4 units). Major post-operative complications based on the Clavien classification occurred in only 2.6% of donor cases compared to 13.8% in non-donors (P < 0.0001). There was one RLDH in-hospital mortality (0.5%) in New York compared to 4.3% after ERH (P = 0.003). CONCLUSIONS: This study represents one of the first unsolicited regional analyses of donor morbidity and resource utilization for RLDH and further emphasizes the need and utility of a live donor registry.

Following primary infection, human herpesvirus 6 (HHV-6) establishes a persistent infection for life. HHV-6 reactivation has been associated with transplant rejection, delayed engraftment, encephalitis, muscular dystrophy, and drug-induced hypersensitivity syndrome. The poor understanding of the targets and outcome of the cellular immune response to HHV-6 makes it difficult to outline the role of HHV-6 in human disease. To fill in this gap, we characterized CD4 T cell responses to HHV-6 using peripheral blood mononuclear cell (PBMC) and T cell lines generated from healthy donors. CD4(+) T cells responding to HHV-6 in peripheral blood were observed at frequencies below 0.1% of total T cells but could be expanded easily in vitro. Analysis of cytokines in supernatants of PBMC and T cell cultures challenged with HHV-6 preparations indicated that gamma interferon (IFN-γ) and interleukin-10 (IL-10) were appropriate markers of the HHV-6 cellular response. Eleven CD4(+) T cell epitopes, all but one derived from abundant virion components, were identified. The response was highly cross-reactive between HHV-6A and HHV-6B variants. Seven of the CD4(+) T cell epitopes do not share significant homologies with other known human pathogens, including the closely related human viruses human herpesvirus 7 (HHV-7) and human cytomegalovirus (HCMV). Major histocompatibility complex (MHC) tetramers generated with these epitopes were able to detect HHV-6-specific T cell populations. These findings provide a window into the immune response to HHV-6 and provide a basis for tracking HHV-6 cellular immune responses.

A protocol consisting of a single donor-specific transfusion (DST) plus a brief course of anti-CD154 monoclonal antibody (anti-CD40 ligand mAb) induces permanent islet allograft survival in chemically diabetic mice, but its efficacy in mice with autoimmune diabetes is unknown. Confirming a previous report, we first observed that treatment of young female NOD mice with anti-CD154 mAb reduced the frequency of diabetes through 1 year of age to 43%, compared with 73% in untreated controls. We also confirmed that spontaneously diabetic NOD mice transplanted with syngeneic (NOD-Prkdc(scid)/Prkdc(scid)) or allogeneic (BALB/c) islets rapidly reject their grafts. Graft survival was not prolonged, however, by pretreatment with either anti-CD154 mAb alone or anti-CD154 mAb plus DST. In addition, allograft rejection in NOD mice was not restricted to islet grafts. Anti-CD154 mAb plus DST treatment failed to prolong skin allograft survival in nondiabetic male NOD mice. The inability to induce transplantation tolerance in NOD (H2g7) mice was associated with non-major histocompatibility complex (MHC) genes. Treatment with DST and anti-CD154 mAb prolonged skin allograft survival in both C57BL/6 (H2b) and C57BL/6.NOD-H2g7 mice, but it was ineffective in NOD, NOD.SWR-H2q, and NOR (H2g7) mice. Mitogen-stimulated interleukin-1beta production by antigen-presenting cells was greater in strains susceptible to tolerance induction than in the strains resistant to tolerance induction. The results suggest the existence of a general defect in tolerance mechanisms in NOD mice. This genetic defect involves defective antigen-presenting cell maturation, leads to spontaneous autoimmune diabetes in the presence of the H2g7 MHC, and precludes the induction of transplantation tolerance irrespective of MHC haplotype. Promising islet transplantation methods based on overcoming the alloimmune response by interference with costimulation may require modification or amplification for use in the setting of autoimmune diabetes.