Islet Transplantation in Mice Differing in the I and S Subregions of the H-2 Complex

Steffes, Michael W.; Nielsen, O; Dyrberg, Thomas; Baekkeskov, Steinunn; Scott, J.K.; Lernmark, Åke

doi:10.1097/00007890-198106000-00017

Cited by 17 publications

(10 citation statements)

References 7 publications

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“…However, other products encoded by genes in or near the immune response region might be present on the beta cells. We have noted that islets transplanted between mice which differ only in certain genes located between the K and D regions are rejected (28). In interpreting these results we cannot rule out the possibility that small amounts of Ia antigens may be present on some or all of the beta cells but at a level 5% to 10% that on lymphocytes.…”

Section: Discussionmentioning

confidence: 88%

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Expression of major histocompatibility antigens on pancreatic islet cells.

Baekkeskov¹,

Kanatsuna²,

Klareskog³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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Insulin-dependent diabetes mellitus is often accompanied by manifestations of autoimmunity and is frequently associated with certain HLA haplotypes, predominantly DR3 and DR4. Because the major histocompatibility antigens are important determinants of the immune response in various tissues, we have investigated their expression on the pancreatic islet cells. Human, mouse, or rat islets ofLangerhans, as well as lymphocytes or other differentiated cells, were biosynthetically labeled with radioactive amino acids, lysed in detergent, and immunoprecipitated with several antisera specific for major histocompatibility antigenic groups. The immunoprecipitates were analyzed by NaDodSo4/ polyacrylamide gel electrophoresis under reducing conditions followed by autoradiography. The major histocompatibility antigens corresponding to the H-2 K,D molecules in mice, the Hi-A in rats, and the HLA-A, -B, and -C in humans were precipitated from both islet and lymphocyte lysates and were accompanied by fi2-microglobulin. Binding of H-2 antibodies to islet cells was also confirmed by a radioligand assay using l'I-labeled protein A and by indirect immunofluorescence. Analyses in the fluorescence-activated cell sorter revealed that >95% of the cells in the beta-cellrich fraction were fluorescent, providing further evidence that the pancreatic beta cells express the major histocompatibility antigens. Monoclonal antibodies or mouse alloantisera against HLA-DR or Ia antigens did not react with labeled pancreatic islet cell proteins.

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Section: Discussionmentioning

confidence: 88%

“…Pancreatic islets were prepared from 5-to 6-month-old male mice by several collagenase digestions followed by discontinuous Percoll (Pharmacia, Uppsala, Sweden) gradient centrifugation (28). Rat islets were isolated by collagenase digestion followed by a Ficoll (Pharmacia) -gradient centrifugation (29).…”

mentioning

confidence: 99%

Expression of major histocompatibility antigens on pancreatic islet cells.

Baekkeskov¹,

Kanatsuna²,

Klareskog³

et al. 1981

Proc. Natl. Acad. Sci. U.S.A.

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“…It has previously been suggested that some cells in the Langerhans' islets express la anti gens [ 16], although endocrine cells seem to be la-negative [1, 3,12]. Passenger lymphocytes or endothelial cells have been suggested to be responsible for the rejection of transplanted murine Langerhans' islets.…”

Section: Discussionmentioning

confidence: 99%

“…However, in experiments with mice differeing only in the H-2 and S regions, SteffeseX al. [16] attribute rejection of Langer hans' islets mainly to la-positive endocrine or nonendocrinc cells in the islets.…”

Section: Introductionmentioning

confidence: 94%

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Distribution of Ia-Positive Cells in the Pig and Human Pancreas

et al. 1984

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Coordinate expression of the endogenous p53 gene in beta cells of transgenic mice expressing hybrid insulin-SV40 T antigen genes.

Efrat

Baekkeskov²,

Lane³

et al. 1987

The EMBO Journal

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The expression of p53 has been evaluated during oncogenesis of the pancreatic beta cells in transgenic mice harboring hybrid insulin‐SV40 T antigen genes. Significant levels of p53 are detected in all cells expressing large T antigen. In contrast, the protein is undetectable in normal beta cells. There is a complete correspondence between the onset of expression of T antigen and the appearance of the endogenous p53 protein. In tumors, the two proteins are found in a complex. In addition, free uncomplexed T antigen is detected in every cell which expresses the transgene. These results are consistent with the participation of p53 in T antigen‐induced tumorigenesis in vivo. The early appearance of p53 in all beta cells expressing large T cannot readily explain the progression of a small fraction of these cells into solid tumors.

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Islet Transplantation in Mice Differing in the I and S Subregions of the H-2 Complex

Cited by 17 publications

References 7 publications

Expression of major histocompatibility antigens on pancreatic islet cells.

Expression of major histocompatibility antigens on pancreatic islet cells.

Distribution of Ia-Positive Cells in the Pig and Human Pancreas

Coordinate expression of the endogenous p53 gene in beta cells of transgenic mice expressing hybrid insulin-SV40 T antigen genes.

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