9%), to the branched-chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) in 6 of 19 patientsOrgan-specific autoimmune diseases are characterized by (31.6%), and to the 2-oxoglutarate dehydrogenase com-the production of autoantibodies and the destruction of speplex E2 (OGDC-E2) in 1 of 19 patients (5.3%). In a compar-cific tissues. Primary biliary cirrhosis (PBC) has been considative study of sera from the same patients, anti-PDC-ered a model autoimmune disease and a paradigm for dis-E2 antibodies were found in 19 of 19 patients (100%), eases such as Hashimoto's thyroiditis 1 and type I diabetes anti-BCOADC in 9 of 19 patients (47.3%), and anti-mellitus. 2 PBC is characterized by destruction of intrahepatic OGDC-E2 in 4 of 19 patients (21.1%) patients. AMA in bile ducts and production of high-titer autoantibodies against bile were always found together with antibodies of cor-mitochondrial autoantigens. 3 Much work has been directed responding specificities in the serum from the same pa-at the detection and characterization of antimitochondrial tient. Immunoglobulin (Ig)A AMA were found in the bile autoantibodies (AMA). Earlier studies from both our laboraof 9 of 19 patients (47.7%) with PBC; they were specifi-tory and others have shown that AMA react with a series of cally directed against PDC-E2 in 8 of 19 patients (42.1%) highly conserved intramitochondrial proteins, in particular and to BCOADC in 2 of 19 patients (10.5%). Epitope map-the 2-oxo acid dehydrogenase complexes, including the dihyping of IgA anti-PDC-E2 antibodies indicated that, like drolipoylacetyltransferase component of the pyruvate dehyserum autoantibodies, the immunodominant epitope is drogenase complex E2 (PDC-E2), the branched-chain 2-oxo directed against the inner lipoyl domain of PDC-E2. The acid dehydrogenase complex E2 (BCOADC-E2), and the 2-prevalence and antigen reactivity of IgA AMA in sera oxoglutarate dehydrogenase complex E2 (OGDC-E2). [4][5][6][7][8][9][10][11] The correlated completely with IgA AMA in bile. Autoanti-major autoantibody reactivity is directed against the 74-kd bodies against nuclear envelope pore proteins (gp210) protein, PDC-E2. were found in 1 of 8 (12.5%) sera of patients with PBC, Although the pathogenesis of PBC remains unknown, utilibut not in bile. Furthermore, and of particular interest, zation of immunohistochemical techniques, monoclonal, combinatorial derived, and experimentally induced rabbit antibodies specific for PDC-E2 has revealed the selective expression of a cross-reactive molecule at the apex of biliary Abbreviations: PBC, primary biliary cirrhosis; AMA, antimitochondrial autoantibodies; PDC, pyruvate dehydrogenase complex; BCOADC, branched-chain 2-oxo-acid dehydrogeepithelial cells of patients with PBC, but not patients with nase complex; OGDC, 2-oxoglutarate dehydrogenase complex; Ig, immunoglobulin; PBS, primary sclerosing cholangitis or autoimmune hepatitis. 12-14 phosphate-buffered saline; SDS, sodium dodecyl sulfate; BHM, bovine heart mitochondrial Furthermore, deposition of immunoglobul...

Porcine and human islet cells express species-restricted complement regulatory proteins, with the human islet cells expressing mainly hCD59. A low expression of hDAF was detected on islet cells from one of five hDAF TG pigs. These islet cells displayed reduced islet cell cytotoxicity in fresh human serum. We conclude that protection from complement-mediated lysis will be important in the context of intraportal pig-to-human islet transplantation, and expression of a human RCA on islet cells should be beneficial in this context.

Gal alpha(1,3)Gal expression is occasionally detectable on adult porcine islet cells, but not as readily and at a lower level, compared with fetal islet cells. Thus, as porcine fetal islets mature to adult islets, the expression of the Gal alpha(1,3)Gal epitope gradually diminishes. Consequently, cytotoxic anti-Gal alpha(1,3)Gal antibodies in human serum play an important role in the lysis of fetal but not adult porcine islet cells.

We used two-color and three-color flow cytometric analysis to study phenotypical activation and functional subsets of T and natural killer cells in the blood and liver tissue of patients with primary biliary cirrhosis, other chronic liver diseases and the blood of healthy subjects. The changes in blood lymphocyte phenotype in patients with primary biliary cirrhosis and other chronic liver diseases were similar and comprised elevated relative or absolute numbers of activated human leukocyte antigen-DR + T subset (CD4+ and CD8+) cells and DR+ natural killer-like (CD16+) cells. B cell (CD19+) numbers were normal. In primary biliary cirrhosis a selective reduction in T cells of suppressor-inducer (CD45RA + CD4 + ) type was registered. The human leukocyte antigen-DR expression among CD4+ T cell subsets was investigated further in primary biliary cirrhosis and healthy controls using triple antibody flow cytometric analysis. Phenotypical cell activation was confined to helper T cells of the primed, memory (CD45RO + CD4+) type. The decrease in suppressor-inducer T cells in primary biliary cirrhosis was paralleled by a reciprocal increase in primed memory T cells. Several significant differences were observed when blood and liver-infiltrating cells from primary biliary cirrhosis patients were compared. In the liver tissue, the CD4/CD8 ratio was decreased, the relative activation of T-subset cells and NK cells was further increased, the suppressor-inducer T subset was further depressed and the primed memory T subset was increased. The cytotoxic T-cell subset (CD11b-) dominated within the CD8+ population. In liver tissue from other chronic liver disease subjects, a lower CD4/CD8 ratio was found compared with primary biliary cirrhosis.(ABSTRACT TRUNCATED AT 250 WORDS)

Our experimental results suggest that the potent antitumor effects of CD154 gene transduction should be considered for immunostimulatory gene therapy for bladder cancer.