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

Genetic factors and environmental factors are thought to be involved in the pathogenesis of insulin-dependent diabetes mellitus Type 1. Viruses, as one environmental factor, may act as primary injurious agents to beta cells or as triggering agents for autoimmunity. Some viruses such as EMC-D and Coxsackie B4 can induce Type 1 diabetes by infecting and destroying beta cells in genetically susceptible mice. In addition, certain species of monkey, such as Patas, show elevated blood glucose levels and depressed insulin secretion after infection with Coxsackie B4 virus. An occasional case of Type 1 diabetes mellitus appears to be associated with the infection of beta cells with Coxsackie B viruses. In addition, Coxsackie B4 virus may also generate viral antigen-specific cytotoxic T cells which may cross-react with a beta cell-specific autoantigen leading to autoimmune Type 1 diabetes. In the case of viral triggering of autoimmune Type 1 diabetes, certain viruses (eg, retrovirus in NOD mice and rubella virus in hamsters and humans) may alter a normally existing beta cell antigen into an immunogenic form or might induce a new antigen, leading to beta cell-specific autoimmune insulin dependent diabetes mellitus. In addition, other viruses (eg, Kilham's rat virus in DR-BB rats) could generate antigen-specific T effector cells which may cross-react with a beta cell-specific autoantigen. In contrast to the induction of diabetes, viruses can prevent the development of diabetes. Inoculation of DP-BB or NOD mice with lymphocytic choriomeningitis virus reduced the incidence of diabetes or prevented the disease by disordering particular lymphocyte subsets.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Induction and prevention of type 1 diabetes mellitus by viruses. 129 46

Experiments with transgenic mice expressing the glycoprotein (GP) of lymphocytic choriomeningitis virus (LCMV) under the control of the rat insulin promoter (RIP) have demonstrated that potentially self-reactive T cells that normally ignore self peptides may nevertheless be induced by self peptides or "cross-reactive" foreign (e.g. viral) peptides that arise in the host in an immunogenic form; once activated these potentially self-reactive T cells may cause autoaggressive diseases (e.g. diabetes). The possibility of vaccinating against such T cell-mediated immunopathological diseases was evaluated in the RIP-GP transgenic mouse line Bln. Any attempt to vaccinate with the self antigen itself (e.g. recombinant vaccinia virus expressing LCMV-GP) failed to protect mice from disease. However, immunization with a recombinant vaccinia virus expressing LCMV-nucleoprotein (vacc-NP) as a non-GP LCMV vaccine was able to modulate the immune response and prevented autoaggressive disease in a MHC-dependent fashion. In contrast, tolerance induction neonatally or, more generally applicable, by lethal irradiation and reconstitution with neo-self antigen-expressing bone marrow cells always resulted in prevention of virally induced diabetes in this model situation.
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PMID:Vaccination or tolerance to prevent diabetes. 144 6

To address the mechanisms of tolerance to extrathymic proteins, we have generated transgenic mice expressing the lymphocytic choriomeningitis viral (LCMV) glycoprotein (GP) in the beta islet cells of the pancreas. The fate of LCMV GP-specific T cells was followed by breeding the GP transgenic mice with T cell receptor transgenic mice, specific for LCMV and H-2Db. These studies suggest that "peripheral tolerance" of self-reactive T cells does not involve clonal deletion, clonal anergy, or a decrease in the density of T cell receptors or accessory molecules. Instead, this model indicates that self-reactive cytotoxic T cells may remain functionally unresponsive, owing to a lack of appropriate T cell activation. Infection of transgenic mice with LCMV readily abolishes peripheral unresponsiveness to the self LCMV GP antigen, resulting in a CD8+ T cell-mediated diabetes. These data suggest that similar mechanisms may operate in several so-called "T cell-mediated autoimmune diseases."
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PMID:Ablation of "tolerance" and induction of diabetes by virus infection in viral antigen transgenic mice. 190 64

A situation in which virus can be used as a therapeutic agent to prevent a lethal autoimmune disease is explored. Nonobese insulin-dependent diabetes (NOD) mice spontaneously develop insulin-dependent diabetes mellitus (IDDM), characterized by lymphocytic infiltration into the islets of Langerhans and beta cell destruction, resulting in hypoinsulinemia, hyperglycemia, ketoacidosis, and death. Infection of NOD mice with lymphocytic choriomeningitis virus (LCMV) aborts the autoimmune manifestations and resultant IDDM. The viruses' effect is on a subset of CD4+ lymphocytes. Ablating this autoimmune diabetes does not significantly alter immune responses to a variety of non-LCMV antigens that require CD4+ lymphocyte participation. The prevention of IDDM associated with viral therapy is maintained throughout the life spans of NOD mice.
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PMID:Viruses as therapeutic agents. I. Treatment of nonobese insulin-dependent diabetes mice with virus prevents insulin-dependent diabetes mellitus while maintaining general immune competence. 197 80

Nonobese diabetic (NOD) mice are the experimental prototype of type 1 insulin-dependent diabetes mellitus (IDDM). These mice develop a characteristic autoimmune lesion in the pancreatic islets of Langerhans, where infiltrating lymphocytes destroy beta cells, resulting in hypoinsulinemia, hyperglycemia, ketoacidosis, and death. This IDDM, which closely resembles that in humans, is prevented by infecting NOD mice with particular strains of lymphocytic choriomeningitis virus (LCMV), including Armstrong 53b, Traub, WE, and Pasteur. In contrast, the LCMV Armstrong 53b variant, Clone 13, fails to abort IDDM. Hence, although Clone 13 establishes a persistent infection that endures throughout the life spans of NOD mice, their hyperglycemia, hypoinsulinemia, and lymphocytic infiltration into the islets of Langerhans still occur. Genetic reassortant viruses generated between the IDDM therapeutic strain of LCMV Pasteur and the nontherapeutic variant, LCMV Clone 13, were used to treat NOD mice. By using such reassortants and both parental strains of virus to infect NOD mice, the prevention of IDDM was mapped to the S RNA segment of LCMV Pasteur.
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PMID:Viruses as therapeutic agents. II. Viral reassortants map prevention of insulin-dependent diabetes mellitus to the small RNA of lymphocytic choriomeningitis virus. 219 Oct 74

BioBreeding Worcester diabetes-prone (BBdp) rats develop insulin-dependent autoimmune-driven diabetes mellitus spontaneously and intravenous administration of 1 x 10(7) p.f.u. of lymphocytic choriomeningitis virus (LCMV) to young adult mice prevents disease. The virus is lymphotropic, binding to and replicating in such cells. BBdp rats fail to generate virus-specific major histocompatibility complex-restricted cytotoxic T lymphocyte (CTL) responses when challenged with this dose or other doses of LCMV, Pichinde virus or vaccinia virus. Yet such rats clear virus effectively and show no evidence of persistent infection. Associated with this clearance of virus and establishment of immunity is the production of neutralizing antibodies. In contrast, diabetes-resistant (BBdr) rats generate virus-specific CTL responses. Furthermore LCMV binds to fewer lymphoid cells of BBdr rats (in comparison to those of BBdp rats) and replicates in fewer lymphocytes (by one order of magnitude) from these rats. Thus, unlike mice in which CTLs play a dominant role in the control of LCMV infection, BBdp rats do not overcome this infection via CTLs. In addition, both the BBdp rats and their BBdr counterpart may provide useful models for determining whether or how individual lymphocyte subsets function in the induction of CTL responses, for the analysis of virus-induced immunosuppression and for the use of viruses or their products as therapeutic modalities.
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PMID:Cytotoxic T lymphocytes do not control lymphocytic choriomeningitis virus infection of BB diabetes-prone rats. 232 8

Lymphocytic choriomeningitis virus (LCMV) infection prevents the usual insulin-dependent diabetes mellitus of aged BB rats (Dyrberg, Schwimmbeck & Oldstone, 1988; Schwimmbeck, Dyrberg & Oldstone, 1988). In this study earlier observations are extended by noting that LCMV infection substantially alters the immune responsesof BB diabetic-prone (dp) rats. The control, uninfected rats make vigorous primary and secondary antibody responses when challenged with keyhole limpet haemocyanin (KLH), human immunoglobulin (HuIg) or sheep red blood cells (SRBC). Such rats fail to mount a primary response to bovine serum albumin (BSA) but do produce a moderate secondary response. They mount good antibody responses to LCMV but fail to generate either primary or secondary LCMV-specific cytotoxic T-lymphocyte (CTL) responses or CTL responses to Pichinde virus. In contrast, BB dp rats acutely infected with LCMV generate no primary immune responses to SRBC, KLH or BSA and only meager responses when challenged with HuIg. They mount secondary responses to KLH, HuIg and BSA that approximate those of their uninfected litter mates, but have a comparatively lower response to SRBC. LCMV binds to and infects lymphocytes of the BB dp rat. Binding is enhanced over that observed with lymphocytes from BB diabetic-resistant (dr) rats, which are able to generate CTL immune responses to LCMV and Pichinde viruses. Hence, lymphocytes from BB dp rats are uniquely susceptible to binding and replication of LCMV. During the acute stage of LCMV infection, a general primary T-cell immunosuppression occurs with respect to a variety of viral and non-viral antigens. Over time, responsiveness to T-cell dependent antigens returns except for the ability to generate CTL responses to LCMV or the autoimmune response(s) required to cause insulin-dependent diabetes mellitus.
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PMID:Inhibition of diabetes in BB rats by virus infection. II. Effect of virus infection on the immune response to non-viral and viral antigens. 233 72

Insulin-dependent diabetes mellitus results from destruction of pancreatic beta cells. Viruses and autoimmunity have been implicated as possible causes of beta cell destruction in genetically predisposed individuals. The evidence for viruses comes largely from experiments in animals, but several studies in humans point to viruses as triggers in the pathogenesis of diabetes in some cases. In animal models, at least 4 different possible mechanisms for virus-induced diabetes have been proposed. The first mechanism is direct cytolytic infection of pancreatic beta cells. One group of viruses, including encephalomyocarditis virus, Mengovirus 2T, and Coxsackie B viruses, can directly infect and destroy pancreatic beta cells independent of autoimmune processes. The second mechanism is triggering of autoimmune responses. In contrast to the encephalomyocarditis virus-induced diabetes, reovirus type 1 and rubella virus seem to be somehow associated with autoimmunity in the genesis of a diabetes-like syndrome in a certain strain of suckling mice and hamsters, respectively. The third mechanism is cumulative environmental insults. The cumulative environmental insults with viruses and beta cell toxic chemicals can result in diabetes in genetically predisposed non-human primates and certain inbred strains of mice. The fourth mechanism is persistent infection. A certain virus, such as lymphocytic choriomeningitis virus, persistently infects murine pancreatic beta cells and produces hyperglycemia. The evidence that viruses cause diabetes in humans is more circumstantial.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Possible mechanisms in the pathogenesis of virus-induced diabetes mellitus. 282 13

The BB rat spontaneously develops an insulin-dependent diabetes mellitus (IDDM) that closely resembles this disease in man. The pathogenesis involves autoimmune destruction of pancreatic beta-cells. In the present study, inoculation of diabetes-prone BB rats at 30 days of age with a lymphotropic variant of lymphocytic choriomeningitis virus significantly reduced the incidence of diabetes. Such virus-inoculated, diabetes-free rats had normal levels of pancreatic insulin and little or no mononuclear cell infiltration in the islets. Virus was recovered from lymphocytes by cocultivation with permissive cells. In contrast, virus was not detected in a wide variety of organs, indicating that infection in BB rats was primarily lymphotropic. PBL analyzed by FACS and monoclonal markers showed a marked reduction of pan-T. Th, and T suppressor/cytotoxic lymphocyte subsets restricted to 4 and 7 days after infection when compared with numbers of lymphocytes in uninoculated diabetes-prone rats. To prevent IDDM, replicating virus was required, because the expected incidence of IDDM in diabetes prone rats inoculated with UV-inactivated virus was equivalent to that of untreated animals. These results suggest that a virus can suppress the autoimmune response that would otherwise have caused IDDM and may be useful as a probe in dissecting the molecular basis of this autoimmune disorder.
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PMID:Abrogation of diabetes in BB rats by acute virus infection. Association of viral-lymphocyte interactions. 328 32

BB rats serve as a model for human insulin-dependent diabetes mellitus (IDDM), since without insulin treatment, most 60-140-d-old animals die within 1 to 2 wk of developing polyuria, polydypsia, hyperglycemia, and hypoinsulinemia. Lymphoid cells accumulate in the islets of Langerhans and beta cells undergo destruction. We report that inoculation of such BB rats with lymphocytic choriomeningitis virus (Armstrong strain, clone 13) reduces over a prolonged period the incidence of IDDM, normalizes the concentration of blood sugar and pancreatic insulin, prevents the mononuclear cell infiltration in the islets of Langerhans, and for a short time after inoculation alters T lymphocyte subsets. Thus, a virus might be programmed to carry out useful functions.
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PMID:Inhibition of diabetes in BB rats by virus infection. 334 48


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