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

Autoimmunity is paradoxically a physiologic phenomenon. One finds in normal sera natural autoantibodies that are encoded by germ line genes. Autoimmunity is at the origin of common and severe diseases such as diabetes mellitus, rheumatoid arthritis, systemic lupus erythematosus and perhaps psoriasis and Crohn's disease. The disease may be due according to cases to exacerbation of physiologic autoimmunity or to appearance of autoreactive clones producing autoantibodies encoded by mutated genes. The respective role of triggering environmental factors and genetic predisposition (HLA and non HLA genes) is not determined. New immunotherapeutic methods, particularly cyclosporine, monoclonal antibodies (against T cells, CD4 and T cell receptor molecules and Ia antigens) and autoantigen-specific vaccination open new major therapeutic perspectives that presage major improvement in the prognosis of these diseases.
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PMID:[Evolution of the concept of autoimmunity and its therapeutic implications]. 267 84

Diabetic patients with the disease duration less than 1 year (group 1 eight patients with diabetes mellitus type I and group 2 seven patients with diabetes mellitus type II) and 8 healthy donors were examined for subpopulations of lymphocytes (CD 3-, CD 4-, CD 8-, CD 20-positive cells, CD4/CD8), expression of activation markers on peripheral blood mononuclears investigated with monoclonal antibodies of BMA and OKT series, and serum neopterin concentration. Group I patients had low CD4/CD8 and increased number of CD 8 cells, 1a/DR-positive lymphocytes (28.6 +/- 7%), OKT9-positive lymphocytes (8.0 +/- 4.7%), activated neopterin synthesis registered neither in group 2 patients nor donors. The number of CD 3 and CD 4 cells was similar in the diabetics and donors. B-lymphocyte level in group 1 patients was on the decrease. Unbalance in lymphocyte subpopulations, increased expression of activation markers and of serum neopterin can be noted in viral infection reflecting impairment of immunoregulating mechanisms in diabetes mellitus type I.
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PMID:[Study of lymphocyte subpopulations and the expression of activation markers in diabetes mellitus types 1 and 2]. 269 22

The mechanism by which islet beta cells are destroyed in type 1 diabetes is still unknown. Because in diabetes the majority of T cells activated in vivo express CD4 and the islet beta cells selectively express the HLA class II antigens needed for recognition by CD4-positive T cells, the possibility that selective damage to islet beta cells may be caused by CD4-positive cytotoxic cells was investigated. Activated T cells were cloned from a newly diagnosed diabetic patient, and many CD4 cytotoxic clones were detected. The clone with the highest cytolytic capacity lysed HLA class II compatible islet cells which had been induced by interferon gamma and tumour necrosis factor to express class II antigens. The specificity of the lysis was demonstrated by use of histoincompatible islets, other histocompatible target cells, and blocking by anti-class-II monoclonal antibodies. The results show that a CD4-positive T cell clone can lyse HLA class II matched islet cells; this process may be important in the pathogenesis of type 1 diabetes.
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PMID:Do CD4-positive cytotoxic T cells damage islet beta cells in type 1 diabetes? 290 68

A double blind study with thymopentin (TP5) and placebo was performed in 49 patients affected by Type 1 and Type 2 diabetes of long duration characterized by a reduction of the CD4/CD8 (helper/suppressor) lymphocyte ratio. TP5 (50 mg) was administered subcutaneously 3 times weekly for 1 month. Total peripheral lymphocytes and functionally different cell subsets were measured throughout the course of the study. Data showed a statistically significant increase of the CD4/CD8 lymphocyte ratio (p less than 0.02) and of the percentage of B lymphocytes (p less than 0.001) only in the TP5 receiving group. No side effects were observed during the study and patients remained well controlled. These results suggests that TP5 may be administered safely to diabetic patients and by improving impaired cell mediated immune parameters TP5 may contribute to prevent the development of infections in these patients.
Diabetes Res 1987 Oct
PMID:Normalization of the CD4/CD8 lymphocyte ratio and increased B lymphocytes in long standing diabetic patients following therapy with thymopentin. 296 99

Twenty-five recently diagnosed insulin-dependent diabetic patients were screened for the presence of activated T lymphocytes using the anti-IL-2 receptor monoclonal antibody; thirteen had elevated levels of activated T lymphocytes. The activated cells were mostly confined to the CD4 subset, with the CD4/CD8 ratio in IL-2 receptor expressing cells averaging 5 +/- 1 (s.d.) compared with 1.3 +/- 0.3 for all T cells. In recent onset insulin-dependent diabetes blood there was no lack of CD4 CD45R+ (suppressor/inducer) T cells. The activated IL-2 receptor, expressing cells belonged to both CD4 subsets, 'helper inducer' (CD44B4) and 'suppressor inducer', (CD42H4).
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PMID:The majority of the activated T cells in the blood of insulin-dependent diabetes mellitus (IDDM) patients are CD4+. 297 27

Spontaneous diabetes in NOD mice has an immunologically mediated cause and is a T cell-dependent process. When diabetic NOD mice are grafted with cultured BALB/c islet tissue, the islet graft is destroyed by disease recurrence in the graft. Disease recurrence is a CD4 T cell-dependent process as determined by in vivo administration of anti-CD4 or anti-CD8 monoclonal antibody prior to the grafting of islet tissue. Cyclosporine functions in the early sequence of T cell activation by regulating the production of messenger RNA for lymphokines synthesis. Cyclosporine does not inhibit the synthesis of lymphokine once the lymphokine message is present in the cell. Thus, we might expect cyclosporine to be relatively inefficient as an agent for the regulation of disease recurrence following transplantation to actively diabetic recipients, and we would expect cyclosporine to be more effective when administered before the onset of the disease. Low-dose cyclosporine treatment can prevent development of the disease when the drug is administered before the onset of disease. Data presented here show that cyclosporine is ineffective in controlling disease recurrence in the islet graft transplanted to actively diabetic animals. Also, when we eliminate CD4 T cells from the diseased animals and graft islet tissue prior to the administration of cyclosporine, we are unable to maintain a graft with low-dose cyclosporine therapy. This result leads us to conclude that, although anti-CD4 treatment controls the expression of the disease process and allows the survival and function of the islet graft, this treatment does not return diseased animals to the prediabetic condition in which the development of diabetes can be controlled by low-dose cyclosporine therapy.
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PMID:Effect of cyclosporine on immunologically mediated diabetes in nonobese diabetic mice. 313 64

Children with newly diagnosed insulin-dependent diabetes mellitus (IDDM) had increased numbers of CD25 positive lymphocytes in peripheral blood and peripheral blood mononuclear cells responded to insulin antigens by proliferation. The CD25 positivity and insulin proliferation were associated to the duration of symptoms before the diagnosis of IDDM. Thus increased numbers of CD25 positive cells were found in 89% and insulin induced proliferation in 100% of patients with symptoms of diabetes of less than 1 week's duration before diagnosis, while CD25 positivity and insulin-induced proliferation were observed in 36% and 29% of children who had had symptoms for 4 weeks or more before diagnosis. Children with IDDM also had increased numbers of CD4 positive T cells in peripheral blood. The frequency of HLA-DR4 and HLA-DR3/4 in diabetic children was higher and that of HLA-DR2 lower than in the normal population. Insulin, islet cell, gastric-parietal cell, thyroid and antinuclear antibodies did not correlate to the duration of symptoms before diagnosis.
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PMID:Insulin responses and lymphocyte subclasses in children with newly diagnosed insulin-dependent diabetes. 328 Jan 82

The ultrastructure of peripheral blood lymphocyte subsets and activated lymphocytes from 5 patients with recent onset insulin-dependent diabetes as identified by monoclonal antibodies (CD4, CD8 and 4F2) and labelled with gold coupled goat anti-mouse IgG are described and depicted. Electron microscopy revealed no differences in appearance between investigated lymphocyte subsets at the single cell level. Activated lymphocytes as defined by an early activation antigen (4F2) do not always have a characteristic appearance nor do they show morphological signs of activation in all cases. We would conclude that it is not possible to recognize different lymphocyte subsets based only on their ultrastructure.
Diabetes Res 1987 Jun
PMID:Ultrastructure of lymphocyte subsets and of activated lymphocytes in type 1 diabetes as defined by monoclonal antibodies and the immunogold technique. 365 17

An adoptive transfer model of insulin-dependent diabetes mellitus (IDDM) in the nonobese diabetic mouse was used to examine the roles of alpha 4-integrin, vascular cell adhesion molecule 1 (VCAM-1); and intercellular adhesion molecule 1 (ICAM-1) in the pathogenesis of autoimmune diabetes. Antibodies specific for both alpha 4-integrin and one of its ligands, VCAM-1, were able to delay onset of diabetes and decrease the incidence of the disease in adoptive transfer studies. This blocking of disease was accompanied by a marked decrease in lymphocytic infiltration of the islets of Langerhans. Furthermore, these antibodies preferentially block entrance of CD4 T cells into the tissue. Antibodies specific for ICAM-1 had little effect on the onset or incidence of IDDM. Thus, we conclude that an alpha 4-integrin-VCAM-1 interaction is important in T cell entry into the islets of Langerhans and in the pathogenesis of IDDM. In addition, the cascade of events leading to T cell transit across endothelium may be different for CD4 and CD8 cells, and may differ depending on the endothelium involved. Our results support the more general conclusion that an alpha 4-integrin-VCAM-1 interaction may be crucial in allowing activated effector CD4T cells to leave the blood and enter tissue to clear infection.
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PMID:The pathogenesis of adoptive murine autoimmune diabetes requires an interaction between alpha 4-integrins and vascular cell adhesion molecule-1. 751 90

The 65-kDa isoform of glutamic acid decarboxylase (GAD65) has been implicated in autoimmune diabetes in NOD mice, but the role of the 67-kDa GAD isoform (GAD67) is less clear. We found that immunization of 4-week-old NOD mice with purified recombinant mouse GAD67 prevented or significantly delayed the onset of diabetes. To further explore this phenomenon, we characterized anti-GAD67 immune responses in naive and GAD-immunized NOD mice. Anti-GAD67 antibodies titers were relatively low in naive mice at all ages, but a single immunization with GAD67 at 4 weeks induced high titers of anti-GAD antibodies by 6 weeks of age. In both 4-week-old and diabetic NOD mice, there were significant endogenous T-cell proliferative responses against purified recombinant mouse GAD67. These T-cell proliferative responses were blocked by anti-I-ANOD and anti-CD4 antibodies. To characterize the anti-GAD T-cell responses in the NOD mice, we established T-cell lines and T-cell clones which recognized GAD67, and we used recombinant subfragments of GAD to localize the predominant T-cell epitopes in GAD67. T-cells from naive NOD mice proliferated in response to all GAD subfragments, whereas T-cells from diabetic mice responded primarily to the COOH-terminal 83 amino acids of GAD67. These results suggest that GAD67 is an autoantigen in IDDM and immunization of prediabetic NOD mice with GAD67 can prevent the onset of diabetes.
Diabetes 1994 Dec
PMID:Immunization with the larger isoform of mouse glutamic acid decarboxylase (GAD67) prevents autoimmune diabetes in NOD mice. 752 93


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