Rat Cytomegalovirus Vaccine Prevents Accelerated Chronic Rejection in CMV-Naïve Recipients of Infected Donor Allograft Hearts.

Cytomegalovirus accelerates transplant vascular sclerosis (TVS) and chronic rejection (CR) in solid organ transplants; however, the mechanisms involved are unclear. We determined the efficacy of a CMV vaccine in preventing CMV-accelerated rat cardiac allograft rejection in naïve recipients of CMV+ donor hearts. F344 donor rats were infected with RCMV 5 days prior to heterotopic cardiac transplantation into CMV-naïve or H2 O2 -inactivated RCMV-vaccinated Lewis recipients. Recipients of RCMV-infected donor hearts rejected at POD59, whereas vaccinated recipients exhibited a significantly prolonged time to rejection-POD97, similar to recipients of uninfected donor hearts (POD108). Although all of the donor hearts were preinfected, the vaccinated recipients had lower graft and PBMC viral loads at POD 7 compared to unvaccinated controls. Adoptive T cell and passive antibody transfers from vaccinated Lewis rats into naïve recipients demonstrate that both T-cell and B-cell arms of the adaptive immune response provide protection against CMV-accelerated rejection. Similar findings were obtained when testing three different adjuvants in passive transfer experiments. We have determined that the timing of the vaccine prior to transplantation and the specific adjuvant play critical roles in mediating anti-viral responses and promoting graft survival. CMV vaccination prior to transplantation may effectively increase graft survival.

Survival of cultured allografts in patients with burns assessed with probe specific for Y chromosome.

The aim of the study was to determine the fate of cultured skin allografts in patients with burns. In situ DNA hybridisation with a Y probe (pHY 2.1) was used to detect cells carrying the Y chromosome (the probe being visualised by the alkaline phosphatase-antialkaline phosphatase method) in biopsy specimens taken from cultured allografts derived from donors of the opposite sex to the recipients (20 patients with burns). Specimens were taken within a week, between one and three weeks, between four and six weeks, and more than six weeks after grafting. Only two of the 27 biopsy specimens contained cells that were the same sex as the donor; both were taken within a week after grafting. In the 25 other specimens the epithelial cells were the same sex as the recipient. Cultured skin allografts showed no evidence of survival in patients with burns, which suggests that they are probably not suitable for long term management of burns but may be useful as short term biological dressings.

Cutaneous leucocyte composition after human allogeneic bone marrow transplantation: relationship to marrow purging, histology and clinical rash.

Immunohistological and morphometric techniques were used to study the skin after marrow transplantation with particular reference to the relationship of marrow purging, the presence of a clinical rash and histological changes to leucocyte numbers and phenotype. Recipients of T-cell-depleted marrow showed significant reductions in CD2+, CD4+ and CD8+ T-lymphocytes in the first 22 d after transplantation but not after this time. T-cell numbers in recipients of unpurged marrow were similar to those of normal donors, indicating a rapid repopulation by cells from the graft. Langerhans cells (CD1+ dendritic cells) and macrophages, on the other hand, were present in similar numbers in both groups of patients within the first 22 d; the former in low and the latter in normal numbers. Biopsies exhibiting graft versus host disease showed increases in CD2+, CD4+ and CD8+ T-lymphocytes with significant lowering of the CD4:CD8 ratio. A proportion expressed markers of activation and HNK1+ cells and macrophages were also increased. Biopsies exhibiting epidermal basal abnormalities only (changes identical to graft versus host disease but without detectable leucocyte infiltration on conventional microscopy) showed a minor increase in macrophages and HNK1+ cells but no other leucocyte alterations to suggest a pathogenetic link with graft versus host disease. Langerhans cells were reduced in these biopsies, however, when taken more than 22 d post-transplant, suggesting that the epidermal changes are associated with Langerhans cell damage or repopulation. We were unable to identify any significant alteration in leucocytes in patients with strong clinical evidence of graft versus host disease but with histologically unremarkable biopsies. Although it is possible that perivascular increases in T-cells and expression of activation markers precede the characteristic histological picture of graft versus host disease the time scale is probably too short to allow diagnostic value.