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Query: UMLS:C0011849 (diabetes)
 277,896 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Diabetes-prone BB (BB-DP) rats express several T cell dysfunctions which include poor proliferative and cytotoxic responses to alloantigen. The goal of this study was to determine the origin of these T cell dysfunctions. When BB-DP rats were thymectomized, T cell depleted, and transplanted with neonatal thymus tissue from diabetes-resistant and otherwise normal DA/BB F1 rats, the early restoration of T cell function proceeded normally on a cell-for-cell basis; i.e., peripheral T cells functioned like those from the thymus donor. Because the thymus in these experiments was subjected to gamma irradiation before transplantation and there was no evidence of F1 chimerism in the transplanted BB-DP rats, it appeared that the BB-DP T cell precursors could mature into normally functioning T cells if the maturation process occurred in a normal thymus. If the F1 thymus tissue was treated with dGua before transplantation, the T cells of these animals functioned poorly like those from untreated BB-DP rats. dGua poisons bone marrow-derived cells, including gamma radiation-resistant cells of the macrophage/dendritic cell lineages, while sparing the thymic epithelium. Therefore, the reversal of the T cell dysfunction depends on the presence in the F1 thymus of gamma radiation-resistant, dGua-sensitive F1 cells. Conversely, thymectomized and T cell-depleted F1 rats expressed T cell dysfunction when transplanted with gamma-irradiated BB thymus grafts. T cell responses were normal in animals transplanted with dGua-treated BB thymus grafts. With increasing time after thymus transplantation, T cells from all animals gradually expressed the functional phenotype of the bone marrow donor. Taken together these results suggest that BB-DP bone marrow-derived cells that are not T cell precursors influence the maturation environment in the thymus of otherwise normal BB-DP T cell precursors.
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PMID:T cell dysfunction in the diabetes-prone BB rat. A role for thymic migrants that are not T cell precursors. 296 42

Insulin-dependent diabetes is caused by the loss of insulin-producing beta cells in pancreatic islets. It has been proposed that aberrant expression of Class II Major Histocompatibility Complex (MHC) molecules on beta cells stimulates an autoimmune attack against beta cell antigens. To test this hypothesis, we generated transgenic mice that express Class II MHC molecules (E alpha d/E beta b, or I-Eb) on beta cells. Diabetes was found in 100% of transgenic progeny from three expressing transgenic mouse lines, but without evidence for lymphocytic infiltrates. Furthermore, T lymphocytes appeared to be tolerant to the transgene I-Eb molecule, despite the absence of expression of I-Eb in the thymus or any other lymphoid tissue. The results suggest that novel expression of Class II MHC molecules on nonlymphoid cells is by itself insufficient to initiate autoimmune responses against tissue-specific antigens.
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PMID:Diabetes and tolerance in transgenic mice expressing class II MHC molecules in pancreatic beta cells. 296 8

The biological basis for autoimmunity and immunoincompetence in the BB rat has yet to be localized. In spite of normal thymic histology, thymocyte subsets and blastogenesis, thymus gland products (thymosins) have yet to be studied. In the present report, thymus gland function was studied by measuring thymosin alpha 1 levels at one time point in the BB rat compared with control rates, and BB rat responses to exogenous thymosin (Thymosin fraction 5) were observed. At five months of age, BB rats had thymosin alpha 1 levels comparable to Lewis and Wistar furth rats. Thymosin fraction 5 increased the ratio of peripheral blood W3/25 positive to OX8 positive cells, but otherwise had no effect on the BB rats' T-cell immunodeficiency, or frequencies of tissue autoantibodies or insulin-dependent diabetes. Although B-lymphocyte counts were normal in BB rats, splenocyte responses to B-lymphocyte mitogens were depressed. However, thymosin fraction 5 improved the BB rat B-lymphocyte blastogenesis to near normal for Mycoplasma neurolyticum. Coupled with our previous work, our results suggest that the immune derangement in the BB rat resides outside the thymus.
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PMID:Thymosin and the spontaneously diabetic BB rat. 297 10

BB rats are prone to develop an autoimmune form of insulin-dependent diabetes mellitus (IDDM) and thyroiditis. Development of autoimmunity is thymus dependent. Previous studies have shown that BB rats lack a population of T cells bearing the RT6 antigen and have very low numbers of suppressor/cytotoxic T cells. In this study, we confirm that BB rats have decreased numbers of phenotypic T suppressor/cytotoxic (Ts/c) cells (OX19+, OX8+ cells) in their lymphoid organs. Moreover, we find that the phenotypic Ts/c cells of BB rats lack apparent cytotoxic activity. These T cells fail to kill allogeneic target cells in a cell-mediated lympholysis assay and fail to generate lectin-dependent cytotoxicity. The addition of interleukin 2, gamma-interferon, and other lymphokines to cultures of BB T cells does not induce functional cytotoxic T lymphocytes. We find that the activated T cells of newly diabetic rats are incapable of killing major-histocompatibility-complex-matched islet cells, despite the ability of these cells to cause IDDM in passive transfer experiments. We conclude that autoimmune disease occurs in BB rats in the absence of functional cytotoxic T cells.
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PMID:Autoimmunity-prone BB rats lack functional cytotoxic T cells. 313 Oct 22

The aim of the present study was to investigate the possible role of the thymus-dependent immune system in the disease mechanisms underlying type 1 (insulin-dependent) diabetes mellitus. Both animal experiments and human studies were carried out. Firstly, a brief historical review is given of the scientific progress within the aetiology and pathogenesis of diabetes mellitus during the last few decades. Mention is made summarily of some elements of the thymus-dependent immune system, and the athymic nude mouse is presented. Three diabetic animal models are reported, viz. two exogenously provoked diabetes models in mice, virus-induced diabetes and diabetes induced by streptozotocin, besides the spontaneously diabetic BB rat. Insofar as the mouse models are concerned, experiments were carried out on both nude mice and normal thymus-intact mice. Encephalomyocarditis virus was used in the virus model and could after inoculation be isolated in large quantities from nude mice as well as normal thymus-intact mice. Only the latter developed diabetes; the C57 mice in the form of glucose intolerance and the BALB/c/BOM mice in the form of elevation of the mean blood glucose values to about threefold normal level. The nude mice exhibited only a very short-lasting virus antibody formation, while in the thymus-intact mice it was possible, as might be expected, to demonstrate high titres of neutralizing virus antibodies for months after the virus inoculation. In the streptozotocin model, where the streptozotocin was administered by repeated small injections, the nude mice developed considerably milder diabetes than the thymus-intact mice. This survey includes other experiments using various forms of immunosuppression (thymectomy, irradiation, treatment with antilymphocyte serum), which together supply evidence that the thymus-dependent immune system is involved in the pathogenesis of diabetes in the two mouse models mentioned as well as in the spontaneously diabetic BB rat, regardless of the different aetiologies in the models. On this background, clinical immunological studies in patients with type 1 diabetes were carried out. Firstly, studies are reported of subpopulations of the peripheral lymphocytes which, after labelling with monoclonal antibodies, were investigated by means of flow-cytometry. The number of cytotoxic/suppressor T-lymphocytes was found to be reduced at the time of diagnosis of type 1 diabetes, but increasing towards normal levels five months later. The helper T-cells were found to be slightly increased at diagnosis as compared with the values in controls, whereas there were no differences in the total T-lymphocyte counts.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The thymus-dependent immune system in the pathogenesis of type 1 (insulin-dependent) diabetes mellitus. Animal model and human studies. 316 May 50

The elemental concentrations in thymocytes from control and diabetic rats were studied by use of the techniques of cryofixation and X-ray microanalysis to determine whether any changes occur in the diseased state. Decreases in the concentrations of the elements P and K were found in thymocytes from the subcapsular and cortical regions of the gland in thymus tissue taken 4 days after the onset of diabetes. A decrease in the concentration of Mg was also found in thymocytes from the subcapsular region of the gland. These changes suggest that the metabolism of thymocytes in vivo is altered in the diabetic animals.
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PMID:A comparison of the elemental concentrations in tissue thymocytes from diabetic and non-diabetic rats. 323 87

Rats of the BB strain develop diabetes mellitus in a high percentage and display a severe T-cell lymphopenia. In order to investigate the role of micro-environmental factors in the T-cell maturation in BB rats the postnatal development of macrophage subpopulations and T-lymphocyte subsets, in addition to the specific immune response in situ, were studied in thymus, spleen and lymph nodes of BB rats. Wistar rats were used as controls. From the day of birth on, a severe reduction was noticed in the macrophage subpopulations in the thymic cortex of BB rats, but not in spleen and lymph nodes, as compared to Wistar rats. The population of T-suppressor/cytotoxic cells (OX8-positive cells) did not increase any longer from Day 10 after birth in the thymic cortex and from Day 14 in spleen and lymph nodes. This is indicative for an intrathymic maturational defect of the OX8-positive cells in BB rats. No deviations could be observed in the development of the T-helper (ER2-positive) cell population. Young adult BB rats were as capable as Wistars of developing a specific immune response to thymus-independent (TI) antigens, but the response to a thymus-dependent (TD) antigen was delayed and decreased. Also the distribution pattern of the specific antibody-containing cells in a TD response in BB rats differed from that in Wistar rats. The ER2-positive cells, although present in normal numbers, may function insufficiently as T-helper cells in BB rats.
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PMID:Neonatal development of lymphoid organs and specific immune responses in situ in diabetes-prone BB rats. 326 12

To determine if thymic macrophages have insulin receptors, alternate sections of rat thymus were stained with FITC-insulin and examined for nonspecific esterase (ANAE) activity. Cells showing a diffuse ANAE staining pattern also bound FITC-insulin. These cells were concentrated in the cortico-medullary border and increased in number following administration of cortisol. Thymic macrophages may be insulin-dependent and therefore could be malfunctional in diabetes.
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PMID:The binding of FITC-insulin to ANAE-positive cells in rat thymus. 328 Mar 36

Mast cells around the thymus of rats stain red with alcian blue and safranin indicating that the mast cells are probably of the peritoneal (connective tissue) type. After the onset of streptozotocin induced diabetes some cells contain both red and blue granules and blue staining cells may appear. X-ray microanalysis of frozen freeze-dried sections from diabetic male CSE Wistar rats showed electron dense granules to have similar amounts of S to normal rat mast cell granules but reduced levels of Na, Mg, P, Cl and K. Two cells also had electron lucent granules with very high levels of Na, Cl, K and Ca and reduced concentrations of S. The differences in elemental composition suggest that the mast cells from diabetic rats are not immature, but are related to the condition of induced diabetes, and that granules of very different composition can occur within a single cell. X-ray microanalysis has given an insight into mast cell granule elemental content which was not possible by conventional biochemical methods.
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PMID:Elemental levels in mast cell granules differ in sections from normal and diabetic rats: an X-ray microanalysis study. 336 63

Class II major histocompatibility (MHC) molecules have an immunoregulatory role. These cell-surface glycoproteins present fragments of protein antigens (or peptides) to thymus-derived lymphocytes (T cells). Nucleotide sequence polymorphism in the genes that encode the class II MHC products determines the specificity of the immune response and is correlated with the development of autoimmune diseases. This study identifies certain class II polymorphic amino acid residues that are strongly associated with susceptibility to insulin-dependent diabetes mellitus, rheumatoid arthritis, and pemphigus vulgaris. These findings implicate particular class II MHC isotypes in susceptibility to each disease and suggest new prophylactic and therapeutic strategies.
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PMID:A molecular basis for MHC class II--associated autoimmunity. 336 86


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