Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autoimmune T-cell responses to peptide determinants of several autoantigens have recently been characterized. These data suggest that, in some autoimmune models, such as experimental autoimmune encephalomyelitis, T-cell responses may diversify from a nested set of peptides to include many other peptide regions. A similar immune phenomenon pertaining to autoimmune diabetes (IDDM) is observed in NOD mice. We have explored a similar pattern of T-cell responses related to age and disease status in NOD mice termed epitope dominance, which describes immune responses toward a pronounced subset of determinants of the autoantigen glutamic acid decarboxylase (GAD). Our studies have identified a total of five GAD epitopes between the 65 and 67 kDa isoforms. The magnitude of T-cell responses to these various determinants was dependent on the stage of disease as well as on whether mice were protected from disease. The T-cell responses of these epitopes in NOD mice correlated with the predicted binding of these peptides to the NOD class II molecule I-Ag7. We therefore propose a model which implicates antigen presenting cells as critical entities in the propagation of dominant responses to the presentation of autoantigens to T cells, particularly in the Th 1 environment of the NOD mouse. This hypothesis presents a new framework for the discussion and interpretation of the kinetics of T-cell responses to different peptide epitopes in autoimmune diseases such as IDDM.
 ...
PMID:Epitope dominance: evidence for reciprocal determinant spreading to glutamic acid decarboxylase in non-obese diabetic mice. 979 69

Several investigators have reported the possibility of gene therapy for experimental autoimmune diseases such as type-1 insulin-dependent diabetes (IDDM), experimental allergic encephalomyelitis (EAE), rheumatoid arthritis (RA), and systemic lupus erythematosus (SLE). Although there are no reports about gene therapies for human autoimmune rheumatic diseases including RA and SLE, we reviewed these experimental therapies for model animals and discussed the possibility of gene therapy for human autoimmune rheumatic disorders as a new therapeutic strategy.
 ...
PMID:[Gene therapy in autoimmune rheumatic diseases]. 1007 22

Interferon-gamma (IFN-gamma) is a pleiotropic cytokine that has been implicated in immunopathogenic mechanisms of a number of inflammatory diseases of autoimmune or infectious disease etiology. However, its exact role is still a matter of debate. In experimental mouse models, IFN-gamma has been shown to exacerbate autoimmune thyroiditis, insulin-dependent diabetes mellitus, and autoimmune neuritis while it confers protection against experimental allergic encephalomyelitis and experimental uveitis. In this study, we generated transgenic rats with constitutive expression of IFN-gamma in the eye to study its paracrine effects and to investigate whether local production of IFN-gamma also confers protection against uveitis in the rat species. We show here that chronic exposure of ocular cells to IFN-gamma results in apoptotic death of retinal ganglion cells, development of chronic choroiditis, formation of retinal in-foldings, and activation of proinflammatory genes. In contrast to its protective systemic effect in the mouse, constitutive secretion of IFN-gamma in the rat eye was found to predispose the development of severe anterior uveitis and induction of retinal degenerative processes that impair visual acuity. Our data underscore the danger in extrapolation of cytokine effects in the mouse to humans without corroborating evidence in other species.
 ...
PMID:Expression of interferon-gamma in the lens exacerbates anterior uveitis and induces retinal degenerative changes in transgenic Lewis rats. 1022 12

In this article, we will examine the roles of transgenic and knockout animals that aid us in understanding two autoimmune diseases-type 1 (insulin-dependent) diabetes and multiple sclerosis. The first sections will focus on studies in type 1 diabetes to show how genetically altered animals have given insight into the role of various immune cell types, autoantigens, co-stimulatory molecules, cytokines and, finally, the role of various effector pathways in the pathogenesis of diabetes. The second section concentrating on the animal model of multiple sclerosis, experimental autoimmune encephalomyelitis (EAE), will show how animals that express a T-cell receptor derived from a clone able to cause disease have given insight into the pathogenesis of EAE.
 ...
PMID:Transgenes and knockout mutations in animal models of type 1 diabetes and multiple sclerosis. 1045 May 11

Experimental allergic encephalomyelitis (EAE) is a T(h)1-type cell-mediated autoimmune disease induced by immunization with myelin proteins and mediated by CD4(+) T cells. Although susceptibility to EAE is dependent largely on MHC background, the B10.S strain is resistant to induction of EAE despite sharing the I-A(s) MHC locus with the susceptible SJL strain. Furthermore, NOD mice which spontaneously develop diabetes are susceptible to EAE induction with myelin oligodendrocyte glycoprotein (MOG) 35-55, whereas a MHC congenic strain, III, which also expresses I-A(g7) MHC haplotype does not develop diabetes and is also resistant to EAE induction. We induced EAE in these four strains of mice with MOG peptides 92-106 (for I-A(s) strains) and 35-55 (for I-A(g7) strains) in complete Freund's adjuvant. In the susceptible strains (SJL and NOD) in vitro, there are high levels of IFN-gamma production, whereas the resistant strains (B10.S or III) secreted primarily IL-4/IL-10 and transforming growth factor (TGF)-beta, and had decreased levels of IFN-gamma. When brains from susceptible and resistant mice were examined by immunohistochemical methods for cytokine expression, the brains from resistant mice showed fewer infiltrates which predominantly expressed IL-4 and IL-10 and/or TGF-beta. Brains from NOD and SJL with EAE showed mainly IL-2 and IFN-gamma positive cells. Thus, resistance to MOG induced EAE in B10.S and III mouse strains is related to non-MHC genes and is associated with an altered balance of pro- and anti-inflammatory cytokines both in lymphoid tissue and in the brain following immunization with myelin antigens.
 ...
PMID:Genetic susceptibility or resistance to autoimmune encephalomyelitis in MHC congenic mice is associated with differential production of pro- and anti-inflammatory cytokines. 1046 78

In the past few years, considerable evidence has accumulated to suggest the existence of functionally polarized responses by the CD4+ T helper (Th)--and the CD8+ T cytotoxic (Tc)-cell subsets that depend on the cytokines they produce. The Th1 and Th2 cellular immune response provide a useful model for explaining not only the different types of protection, but also the pathogenic mechanisms of several immunopathological disorders. The factors responsible for the polarization of specific immune response into a predominant Th1 or Th2 profile have been extensively investigated in mice and humans. Evidence has accumulated from animal models to suggest that Th1-type lymphokines are involved in the genesis of organ-specific autoimmune diseases, such as experimental autoimmune uveitis, experimental allergic encephalomyelitis, or insulin-dependent diabetes mellitus. Accordingly, data so far available in human diseases favor a prevalent Th1 lymphokine profile in target organs of patients with organ-specific autoimmunity. By contrast, Th2-cell predominance was found in the skin of patients with chronic graft-versus host disease, progressive systemic sclerosis, systemic lupus erythematosus, and allergic diseases. The Th1/Th2 concept suggests that modulation of relative contribution of Th1- or Th2-type cytokines regulate the balance between protection and immunopathology, as well as the development and/or the severity of some immunologic disorders. In this review, we have discussed the paradigm of Th1 and Th2 cytokines in relation to autoimmunity and allergy.
 ...
PMID:The paradigm of Th1 and Th2 cytokines: its relevance to autoimmunity and allergy. 1058 Jun 39

Copolymer 1 (Cop 1) inhibits experimental allergic encephalomyelitis induced by a variety of myelin proteins, but has been found ineffective so far in inhibiting other experimental autoimmune diseases such as diabetes or arthritis. Here, we report for the first time that Cop I inhibits the development of experimental autoimmune uveoretinitis, induced in mice by interphotoreceptor retinoid-binding protein (IRBP). Pooled data of three experiments showed that treatment with Cop 1, at 0.5 mg/mouse, reduced the disease severity by 53% ( p = 0.0002). Cop 1 treatment also inhibited the proliferation and the production of cytokines by lymph node cells in response to IRBP and moderately reduced the antibody response to this antigen. The possible mechanisms of EAU inhibition by Cop 1 are discussed.
 ...
PMID:Copolymer 1 inhibits experimental autoimmune uveoretinitis. 1069 14

The environment in which the encounter of antigen with the immune system occurs determines whether tolerance, infectious immunity, or autoimmunity results. Geographical areas with low supplies of vitamin D (for example Scandinavia) correlate with regions with high incidences of multiple sclerosis, arthritis, and diabetes. The active form of vitamin D has been shown to suppress the development of autoimmunity in experimental animal models. Furthermore, vitamin D deficiency increases the severity of at least experimental autoimmune encephalomyelitis (mouse multiple sclerosis). Targets for vitamin D in the immune system have been identified, and the mechanisms of vitamin D-mediated immunoregulation are beginning to be understood. This review discusses the possibility that vitamin D status is an environmental factor, which by shaping the immune system affects the prevalence rate for autoimmune diseases such as multiple sclerosis, arthritis, and juvenile diabetes.
 ...
PMID:Vitamin D and autoimmunity: is vitamin D status an environmental factor affecting autoimmune disease prevalence? 1071 34

Autoimmunity arises when the immune system no longer tolerates self and precipitates lymphocyte reactivity against our own antigens. Although the developing T cell repertoire is constantly purging, self-recognition events do exist when such tight control is evaded and autoreactive lymphocytes escape the thymus (the sites of T cell development) and migrate to the periphery. Upon activation these autoreactive cells may exert aggressive behavior toward one's own tissues and organs leading to autoimmune disease. Multiple sclerosis, Rheumatoid arthritis, and type I diabetes are autoimmune diseases mediated by autoreactive T cells. A logical approach to prevent such autoimmunity would be to reprogram those lymphocytes to tolerate the self antigen. Injection of antigen at the neonatal stage promotes a state of tolerance such that successive encounter with antigen does not precipitate aggressive reactions. The mechanism underlying neonatal tolerance involves priming of T cells whose effector functions do not cause inflammatory reactions upon recognition of antigen but rather induce protective immunity. This form of tolerant immunity provides an attractive strategy for vaccination against autoimmunity. Herein, it is shown that neonatal exposure to a self-peptide-immunoglobulin chimera drives a tolerant immunity toward the self-peptide and protects against the autoimmune disease, experimental allergic encephalomyelitis.
 ...
PMID:Neonatal tolerant immunity for vaccination against autoimmunity. 1076 11

The active vitamin D metabolite, 1,25-dihydroxyvitamin D3[1,25-(OH)2D3], exerts immunosuppressive activity. At a cellular and molecular level, the hormone preferentially targets helper T cell activity (Th1) by inhibiting the secretion of both IL-2 and IFN-gamma by Th1 and by suppressing the secretion pro-Th1 cytokine IL-12 by antigen-presenting cells. The active metabolite further inhibits class II antigen expression and enhances suppressor cell activity. In animal models of autoimmunity, 1,25-(OH)2D3 prevents the development of experimental autoimmune encephalomyelitis, reduces the incidence of diabetes, and attenuates murine lupus. The hormone also prolongs graft survival in animal models of transplantation. In humans, non-classical use of 1,25-(OH)2D3 has led to an anti-proliferative effect in psoriasis, antineoplastic effect in prostate cancer, and immunomodulatory effect in scleroderma. The development of less hypercalcemic analogs might open a new therapeutic area for vitamin D3.
 ...
PMID:1,25-Dihydroxyvitamin D3--a hormone with immunomodulatory properties. 1076 31


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>