T. Howard

Serological evidence of past hepatitis B infection in liver donor and hepatitis B infection in liver allograft

The presence of hepatitis B surface and core antibodies (anti-HBs and anti-HBc) in a liver donor without hepatitis B surface antigen is taken to indicate resolution of hepatitis B and is not considered to contraindicate donation. We report a liver transplant recipient who developed hepatitis B after such a donation. It seems that hepatitis B virus can reside in the liver of a patient who has seemingly recovered from his disease. We recommend avoidance of liver transplants from donors who are positive for anti-HBs and anti-HBc.

Mercury poisoning associated with hepatitis-B immunoglobulin.

as a preservative. We encountered mercury toxicity, in a patient who received high-dose immunoprophylaxis. A 44-year-old man with decompensated cirrhosis from hepatitis B underwent liver transplantation. He received 50 mL HBIG (HyperHep, Miles Inc, Cutter Biological, Elkhard, Indiana, USA) during operation, 50 mL postoperatively and on days 2 and 3. On day 4, he became hepatitis-B surface-antibody (HBsAb) positive, and was put

The domino transplant: transplant recipients as organ donors.

The success of solid organ transplantation is limited by ongoing problems with organ availability. The use of extended cadaveric donors as well as the use of living donors are both strategies used to overcome this shortage. One group of potential donors that has not been previously reported are those who have previously received an organ transplant. This type of transplant was first described as a domino transplantation of heart-lung and heart (1). A combined heart-lung transplant was performed in a patient with end-stage lung disease, but who still had adequate heart performance. The normal heart of this heart-lung recipient was then transplanted into a second patient with end-stage heart disease. In similar types of procedures, the successful retransplantation of a liver allograft from a liver recipient who suffered brain death has been described, as well as retransplantation of a renal allograft (2, 3). The transplantation of kidneys from a heart transplant recipient who suffered brain death has also been reported (4). To obtain a better understanding of the scope and results as such procedures, we performed a comprehensive review of the United States experience (5).

LIVER TRANSPLANT RECIPIENT SERA DERIVED SOLUBLE HLA MEDIATES ALLELE SPECIFIC CTL APOPTOSIS

BACKGROUND Significant levels of donor soluble human leukocyte antigen (HLA) class I (sHLA) are present in patients after transplants. We investigated the possibility that sHLA may inhibit cytolytic T lymphocyte (CTL) activity by inducing apoptosis of the CTL, thereby serving as a mechanism for specific tolerance. METHODS sHLA-A2 and A3 were isolated from the sera of liver transplant recipients by affinity chromatography. T cell bulk lines directed against HLA-A2 and HLA-A3 were generated by stimulation with HLA-A2, A3+ peripheral blood leukocytes and B-lymphoblastoid cells. Induction of T cell apoptosis by sHLA was analyzed by adding sHLA to allospecific CTL 4 or for 24 hr before flow cytometric analysis of propidium iodide and fluorescein isothiocyanate-conjugated annexin V stained cells. T cell receptor (TCR) engagement by sHLA was demonstrated using a monoclonal antibody specific for the TCR. RESULTS sHLA-A3 inhibited CTL activity of a HLA-A3 T cell line by 53%, whereas sHLA-A2 had no effect. sHLA-A3 also increased T cell death by 77% over the control, whereas sHLA-A2 had no significant effect. However, sHLA-A2 induced 21% apoptosis of an anti-HLA-A2 T cell line, whereas sHLA-A3 caused only 3% apoptosis. The antibody complexed form of sHLA was ineffective in the induction of apoptosis. Preincubation of the T cells with anti-T cell receptor monoclonal antibody protected the T cells from sHLA-induced apoptosis, indicating that sHLA-TCR engagement is necessary for this process to occur. CONCLUSION TCR-mediated apoptosis of alloreactive CTL may serve as a mechanism by which sHLA can modulate the immune response.

The role of indirect antigen recognition in islet xenograft rejection

PORCINE pancreatic islets are considered a viable source of insulin-producing tissue for the treatment of Type 1 diabetes mellitus. For this therapy to become a reality, a detailed characterization of human immune responses to porcine islets should be carried out. Our recent studies characterized the mechanism of porcine islet xenograft rejection by human CD41 T cells generated against porcine islets both by in vitro stimulation and in vivo using severe combined immunodeficient mice reconstituted with human peripheral blood leukocytes and transplanted with porcine islets. These studies concluded that a majority of human CD41 T cells recognized porcine MHC molecules as xenoantigens presented by self-antigen presenting cells (APC). To further define the mechanisms of islet xenograft rejection, we transplanted porcine islets under the kidney capsules of streptozotocin-treated C57BL/6 (BL/6), CD4 Knockout (KO), and CD8KO mice, and islet rejection was analyzed. Similarly, BL/6, CD4KO, and CD8KO mice were treated with anti-CD4 or anti-CD8 depleting monoclonal antibodies (mAb), transplanted, and monitored for rejection. To further document the role of CD41 T cells in the response to porcine islets, we studied specific T-cell proliferation to islet antigens in vitro and its requirement of APC for maximum stimulation. In addition, antibody response to porcine xenoantigens in each group of transplanted mice was measured.