In Situ Ultrastructural Demonstration of Cells Bearing la Antigens in the Murine Pancreas

Farr, Andrew G.; Anderson, Susan K.

doi:10.2337/diab.34.10.987

Cited by 6 publications

(4 citation statements)

References 9 publications

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“…The purified cell fraction is composed of intact cells with a membranous la expression for >80%. Ultrastructurally, the isolated la-positive islet cells do not resemble any of the typical endocrine islet cell types, which agrees with in situ observations in the normal rat pancreas (13,14); rather, they present the morphologic features of monocytic cells from myeloid origin. However, it cannot be concluded from the electron micrographs whether they correspond to phagocytic macrophages or antigen-presenting dendritic cells, because this classification requires further histochemical, functional, and immunochemical analyses (20).…”

Section: Discussionsupporting

confidence: 86%

“…However, it cannot be concluded from the electron micrographs whether they correspond to phagocytic macrophages or antigen-presenting dendritic cells, because this classification requires further histochemical, functional, and immunochemical analyses (20). That the two cell types may be present has been suggested by earlier work on intact islet tissue (11, [13][14][15]. The availability of purified la-positive islet cells can bring conclusive evidence after a systematic assessment of the typical and differentiating features of both cell types.…”

Section: Discussionmentioning

confidence: 82%

“…Granulelike inclusions have not been described in lapositive islet cells that were examined in situ (13,14). They have probably been ingested from dead cells and cellular debris produced during the isolation procedure.…”

Section: Discussionmentioning

confidence: 99%

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Presence of Pancreatic Hormones in Islet Cells With MHC-Class II Antigen Expression

et al. 1987

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In the normal rat pancreas, only few islet cells express MHC-class II antigens. Their nature and function has not yet been elucidated. We report a method for the purification of Ia-positive islet cells by fluorescence-activated cell sorting. The isolated mononuclear cells appear of nonendocrine origin but contain vacuoles with partially digested secretory vesicles. Both insulin- and glucagon-immunoreactive granules were identified in these vacuoles of varying size and composition. It is suggested that at least part of the rat islet cells with class II antigen expression can exhibit phagocytotic properties leading to the uptake of fragments from damaged endocrine cells. This functional characteristic may implicate this particular islet cell type in the pathology of the endocrine pancreas in type I diabetes.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 82%

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Presence of Pancreatic Hormones in Islet Cells With MHC-Class II Antigen Expression

et al. 1987

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“…The selected strain combination thus led to rapid rejection of untreated donor islet tissue and was, in this respect, comparable to previously used models for islet transplantation across an MHC barrier (7,8,11,23). The immunogenicity of islet allografts has been attributed to the presence of passenger leukocytes (3,24), particularly the MHC class II-positive lymphoid cells, which are located in the islet interstitium (25). Because of the estimated number of islet cells with surface MHC class II positivity (p. 908), each implant of freshly isolated rat islets can be expected to introduce -2.10 4 of these cells, a number at which dendritic cells can induce immune responses in the rat (6).…”

Section: Discussionmentioning

confidence: 53%

Transplantation of Purified Islet Cells in Diabetic Rats: II. Immunogenicity of Allografted Islet β-Cells

et al. 1991

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This study examines whether the survival of allografted rat islet beta-cells is influenced by the presence of other pancreatic donor cells. Grafts (RT1u/l) of different cellular composition were intraportally transplanted in streptozocin-induced diabetic rats (RT1n/n). All grafts corrected the diabetic state within 3 days. Implants of freshly isolated islets contained various endocrine and nonendocrine cell types; they became diffusely infiltrated within 1 wk and were completely destroyed within 2 wk. A 4-day culture period did not lead to major changes in the cellular composition of the islets or in their survival as allograft. Islet cell aggregates prepared after islet dissociation and cell purification were less acutely infiltrated and less rapidly rejected. Aggregates composed of sorted MHC class II-negative cells maintained basal normoglycemia in 3 of 5 recipients for 5 wk but only in 1 of 5 for 20 wk. Aggregates of purified islet beta-cells remained relatively free of diffuse infiltrations during the 1st wk and preserved the normalized state in 7 of 13 recipients for 5 wk; after 20 wk, 6 of 13 were still aglucosuric, but 40% of the implants were diffusely infiltrated and depleted of insulin. Reaggregation of purified islet beta-cells with purified islet endocrine non-beta-cells promoted their long-term survival as allograft: 11 of 13 recipients of mixed islet endocrine cells maintained normal basal glycemia over 20 wk; their implants contained relatively constant insulin reserves and remained virtually devoid of diffuse infiltrations. These results demonstrate that techniques aiming at the elimination of surface MHC class II-positive cells are less successful in preparing rat islet allografts of low immunogenicity than methods of positive cell selection. Pure islet beta-cells are immunogenic as an allograft but illicit a milder and less-acute immune attack than undissociated islet tissue. Nonendocrine and damaged islet cells are suspected of enhancing the rapidity and intensity of the cytotoxic reaction. Survival of allografted beta-cells is markedly prolonged by the presence of islet endocrine non-beta-cells within the graft. The mechanisms underlying this effect have not yet been elucidated; they may involve immune and metabolic interactions of the endocrine non-beta-cells. We conclude that purification of islet endocrine cells represents a new and powerful method for preparing insulin-producing allografts that can survive in hosts without pharmacological immunosuppression.

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Islet morphologic changes

Gepts

Veld

1987

Diabetes Metab. Rev.

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In Situ Ultrastructural Demonstration of Cells Bearing la Antigens in the Murine Pancreas

Cited by 6 publications

References 9 publications

Presence of Pancreatic Hormones in Islet Cells With MHC-Class II Antigen Expression

Presence of Pancreatic Hormones in Islet Cells With MHC-Class II Antigen Expression

Transplantation of Purified Islet Cells in Diabetic Rats: II. Immunogenicity of Allografted Islet β-Cells

Islet morphologic changes

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