Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004364 (autoimmune disease)
 24,845 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Peripheral blood (PB) T cells from 56 patients with B-cell chronic lymphocytic leukemia (B-CLL) were analyzed by two- and three-color immunofluorescence (IF) to determine the expansion of distinct T-cell subsets and their relationship with the clinical and biological features of the disease. We detected the expansion of an unusual T-cell subpopulation expressing lower CD4 or CD8 levels (CD4lo, CD8lo) than classic T cells (CD4hi, CD8hi). This subpopulation also expressed low levels of the CD3/TCR alpha/beta complex and was CD19-CD13-CD14-. A phenotypic analysis probing the activation level of CD4lo, CD8lo, CD4hi, and CD8hi cells showed that they comprised increased counts of HLA-DR+, CD11b+, CD45R0+, and CD45RA+ cells. Subset expansion ranged from 2.1- to 13.6-fold. Statistical analysis showed that the size of some of these subsets was correlated to intrinsic features of the tumor. First, CD4loHLA-DR+ cell counts were higher in patients with stage A than those with stages B and C disease. Second, CD8loHLA-DR+ cell counts were higher in patients in stable remission than in those at diagnosis. Third, CD4loHLA-DR+, CD4loCD45R0+, CD4loCD45RA+, and CD4hiCD11b+ cell counts were higher in patients whose tumor cells expressed high levels of surface immunoglobulin (sIg) than in those expressing low levels. The involvement of CD4lo and CD8lo cells in most of these correlations suggests that they may be tumor-reactive cells. Similar cells described in human and murine autoimmune disease have been shown to be autoreactive anergic cells, which may derive from nonclassic pathways of T-cell development.
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PMID:Expansion of T cells expressing low CD4 or CD8 levels in B-cell chronic lymphocytic leukemia: correlation with disease status and neoplastic phenotype. 790 42

T cells that recognize autoantigens may play a central role in the autoimmune response. We have previously shown that autoantigen-reactive T cells (CD4+) to U1-small nuclear ribonucleoprotein A were found in the PBMC of patients with systemic lupus erythematosus or mixed connective tissue disease. To reveal clonotypes of such T cells that spread to the periphery, T cell clonal accumulations and their TCR-beta chain variable gene usages in fresh PBMC from eight patients with mixed connective tissue disease were analyzed by a new method of single strand conformation polymorphism applying to TCR gene detection. The results revealed that the numbers of accumulated T cell clones (mean: 24.3 clones) were greater than the numbers of clones detected in healthy donors (mean: 4.0 clones). Frequently used V beta genes in these accumulated T cell clones were V beta 1, 3, 4, 5.2, 14, and 16. After the stimulation for these samples with the soluble recombinant U1-small nuclear ribonucleoprotein A protein, proliferative T cell responses were observed. We found that T cell clones expressing more restricted TCR V beta genes (1, 3, 5.2, and 14 families) accumulated in vitro. These results suggest that autoantigen-reactive oligoclonal T cell accumulations are present in the peripheral blood from systemic autoimmune disease patients.
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PMID:Clonotype analysis of peripheral blood T cells and autoantigen-reactive T cells from patients with mixed connective tissue disease. 793 May 95

Multiple sclerosis (MS) is thought to be an autoimmune disorder, mediated by myelin-specific T cells. Recent studies demonstrate that activated T cells specific for MBP are increased in MS, and that the MBP-specific T cells and T cell infiltrates in MS brains conserve homologous TCR CDR3 motifs. Since the CDR3 motifs are also shared by encephalitogenic T cells inducing EAE, it is likely that therapeutic strategies effective for EAE may be useful for MS. In this review, I discuss the possible application of TCR vaccination, TCR antagonist peptides and oral tolerization. Considering the chronic relapsing features of MS, treatments which are safe and may tighten the immune regulatory networks are recommendable.
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PMID:[New strategies for treatment of multiple sclerosis based on the autoimmune pathogenesis]. 799 5

Type I diabetes is an autoimmune disease characterised by a marked activation of peripheral T cells around the time of clinical diagnosis. Studies of T-cell antigen receptor V beta (TCRBV) gene usage in type I diabetes have been conflicting. Using a semi-quantitative polymerase chain reaction technique and flow cytometry we have investigated the TCRBV gene usage of 13 newly diagnosed patients with type I diabetes and 11 normal healthy controls. No preferential TCRBV gene usage was found between patients and controls even after matching for HLA-DR3 and/or -DR4. In addition, no significant differences in TCRBV gene usage were found between sequential samples taken over a period of up to 7 months following diagnosis. These results suggest that the TCR repertoire of these patients is heterogeneous and it is unlikely that a single 'pathogenic' T-cell clone is dominant at the clinical onset of the disease.
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PMID:Analysis of the peripheral T-cell receptor V beta repertoire in newly diagnosed patients with type I diabetes. 799 59

In this review, we describe an anti-idiotypic regulatory mechanism that is naturally induced by the autoimmune disease process, and that can be boosted by injection of TCR peptides that mimic epitopes generated naturally from germline sequences. The striking similarities in the induction and characteristics of rodent and human T cells specific for TCR peptides support the generality of the observation, and enhance the probability that this immunoregulatory mechanism will have application in human organ-specific autoimmune diseases that are characterized by oligoclonal expression of TCR V genes. The major challenges that remain to be resolved to make the TCR peptide therapy more widely applicable include (1) establishing disease-relevant V gene biases in individual patients, (2) identifying biologically active TCR peptide sequences, and (3) demonstrating that the induction of anti-TCR peptide immunity in humans can reduce the pernicious activity of autoreactive T cells putatively directed at organ-specific target antigens.
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PMID:Immunity to T cell receptor peptides: theory and applications. 805 14

Autoimmune diseases can be characterized by increases in Th cell activities, suggesting that inhibition of Th cell function might ameliorate autoimmunity. We have recently reported that administration of nonmitogenic anti-CD3 mAb (nmCD3) to nonautoimmune mice can induce long-term Th cell hyporesponsiveness, reflected by reduced IL-2 secretion upon re-exposure to Ag. This study was designed to determine the effects of nmCD3 on autoimmunity by using the murine collagen-induced arthritis model. Treatment of DBA/1 mice with nmCD3 delayed the onset and reduced the severity of arthritis in mice immunized with type II collagen (CII). This effect was not caused by depletion of T cells or modulation of TCR. The observed inhibition of arthritis was not caused by decreased Ab production, as anti-CII titers were not affected. Rather, lymph node cells from CII-immunized mice treated with nmCD3 were hyporesponsive to in vitro stimulation with CII. This hyporesponsiveness was reflected by a marked decrease in secretion of IL-2 and IFN-gamma, but not of IL-4, which suggests that nmCD3 had its principal effect on Th1 cells. The hyporesponsiveness was not Ag-specific, because IL-2 and IFN-gamma production in response to a pan-T cell mitogen was also reduced. These results demonstrate that induction of Th1 cell hyporesponsiveness with nmCD3 can significantly alter the course of CIA and suggest that IL-2 and/or IFN-gamma play a crucial role in disease pathogenesis.
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PMID:Induction of T helper cell hyporesponsiveness in an experimental model of autoimmunity by using nonmitogenic anti-CD3 monoclonal antibody. 808 1

The present study examined the mechanism(s) of tolerance induction for intestinal intraepithelial lymphocytes (iIELs) using an alloantigen (Ag)-specific gamma/delta T cell receptor (TCR gamma/delta) transgenic (Tg) model. In Tg Ag-bearing H-2b/d mice (Tgb/d), Tg iIELs were Thy-1-, CD44+, CD45R (B220)+, and CD5+, whereas in syngeneic Tgd/d mice, iIELs were Thy-1+, CD44-, and CD45R- with a subset of CD5+ cells. Previously, we had shown that tolerance for Tgb/d iIELs involved functional anergy and deletion (Barrett, T. A., M. L. Delvy, D. M. Kennedy, L. Lefrancois, L. A. Matis, A. L. Dent, S. M. Hedrick, and J. A. Bluestone. 1992. J. Exp. Med. 175:65). In this study we demonstrate that Tgb/d iIELs expressing dull levels of Thy-1 proliferated in the presence of exogenous rIL-2. A direct precursor-product relationship between the Thy-1+-responsive iIELs and the tolerant Thy-1dul/- iIELs was demonstrated by adoptive transfer into severe combined immunodeficient (SCID) mice. Tg Thy-1+ iIELs reconstituting Ag+ but not Ag- SCID mice downregulated Thy-1 after Ag exposure in vivo. Analysis of bone marrow (BM) chimeras demonstrated the persistence of Tg IELs in all Ag+ chimeras although a modest degree of clonal deletion was apparent. The greatest percentage of Tg IELs were detected when Ag was restricted to radioresistant cells (e.g., epithelial cells) compared with BM-derived antigen-presenting cells (APC). This was especially apparent in thymectomized chimeric mice. Consistent with the notion that Ag-bearing epithelial cells may be poor APC, isolated intestinal epithelial cells from Ag-bearing mice failed to stimulate Tg iIELs compared with splenic APC. These studies suggest that the major population of TCR gamma/delta iIELs were probably extrathymically derived and encountered self-Ag on intestinal epithelial cells. The induction of tolerance likely involved an activation event resulting in downregulation of Thy-1. These mechanisms of tolerance for TCR gamma/delta iIELs led to the persistence of a reservoir of self-reactive T cells with the potential for mediating autoimmune disease.
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PMID:Tolerance of T cell receptor gamma/delta cells in the intestine. 809 32

Over the past decade, there was considerable scepticism regarding the existence, nature, and function of suppressor T (Ts) lymphocytes, particularly antigen-specific Ts lymphocytes. The receptors of putative antigen-specific murine Ts hybrids revealed that most either lacked the T cell receptor beta (TCR beta) chain or had failed to properly rearrange them and thus could not make a functional receptor. Moreover, studies of the DNA of sequences of the MHC I-J region (considered an important determinant for suppression) fail to show evidence for a unique open reading frame capable of encoding the I-J restriction element. In addition, no molecular basis for suppression had been characterized. These criticisms have now been satisfactorily resolved and the pendulum is swinging in favor of participation by antigen-specific Ts lymphocytes in immune tolerance. Ts lymphocytes have now been cloned and cell lines have been found to be idiotypic-specific. Indeed, specific Ts lymphocytes in the periphery have been shown to prevent the appearance of autoreactivity. It is, therefore, legitimate to consider their control as part of the mechanisms of maintaining the integrity of the immune system. Moreover, all human primary Ts clones and the majority of murine Ts clones have now been shown to rearrange TCR alpha beta. Ts lymphocytes are induced by antigen via antigen-presenting cells (APCs), and may do so in the context of MHC class II antigens, a concept not previously accepted. Moreover, there is now considerable evidence that such cells many well be involved in various autoimmune disease states.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Suppressor T lymphocyte dysfunction is important in the pathogenesis of autoimmune thyroid disease: a perspective. 811 29

Thymectomy of 3-day-old mice induces organ-specific autoimmune disease. To define a relationship between the development of T cells early in the neonatal period and autoimmunity, we studied the thymus and peripheral lymphoid tissues of 3-day-old mice. Lymph nodes, but not spleens, of 3- to 4-day-old mice contained a significant number of thymus-derived CD4+CD8+ cells that are phenotypically similar to CD4+CD8+ thymocytes in their level of expression of CD3 and HSA. It is likely that the prematurely exported cells are the progenitors of autoreactive T cells because the lymph nodes from 3- to 4-day-old male, but not female, mice which express a transgenic TCR specific for the H-Y Ag contained a large number of CD4+CD8+Tg+ as well as CD4-CD8+Tg+ T cells. Thus, the neonatal thymus is capable of exporting immature T cells that in the absence of a thymus may differentiate into autoimmune effector cells.
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PMID:Premature escape of double-positive thymocytes to the periphery of young mice. Possible role in autoimmunity. 812 Mar 65

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease that can be induced by the adoptive transfer of CD4, myelin basic protein (MBP)-specific T cells. Superantigens activate T cells expressing appropriate TCR V genes. In this study, MBP-specific T cells activated in vitro with a superantigen, staphylococcal enterotoxin B (SEB), could adoptively transfer a severe form of EAE in (PLxSJL)F1 mice, but did not transfer disease in PL/J or SJL/J mice. SEB treatment of donor mice anergized MBP-specific T cells using V beta 8 in (PLxSJL)F1 mice, because subsequent in vitro activation with SEB resulted in a marked decrease in proliferation to SEB and inability to transfer EAE. However, donor cells from (PLxSJL)F1 mice immunized with MBP/CFA that had been exposed to SEB in vivo before MBP stimulation in vitro still produced EAE in recipient mice. To confirm that non-V beta 8 T cells could transfer disease, donor mice were treated with antibody that eliminated V beta 8 T cells; MBP-activated T cells from these mice could still transfer EAE. Finally, EAE induced by SEB-activated T cells was substantially reduced in mice receiving anti-V beta 8 therapy in vivo. The ability of superantigens to activate encephalitogenic T cells may have relevance to human diseases such as multiple sclerosis.
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PMID:Superantigen modulation of experimental allergic encephalomyelitis: activation of anergy determines outcome. 812 Apr 6


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