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)

We previously reported that infection of BALB/c mice with the parasite Plasmodium chabaudi induces high production of natural autoantibodies. Here we demonstrate that such an infection of lupus-prone (NZB x NZW)F1 (B/W) mice retards the development of their autoimmune disease. Survival and disease hallmarks (high-grade proteinuria and IgG anti-DNA antibodies) were delayed for 6 months when parasite inoculation was given at either 3 or 7 months of age, i.e. before or after the onset of the clinical symptoms. Similar beneficial effects, although less pronounced, were obtained when mice were treated with a total of 800 micrograms of IgG (P-IgG) or IgM (P-IgM) or 300 micrograms of cryoglobulin preparations isolated from P. chabaudi-infected BALB/c mice while similarly prepared fractions from uninfected mice had little effect. Compared to these fractions, P-IgG and P-IgM contained higher levels of natural antibodies bearing the D23 idiotype characteristic of polyreactive natural autoantibodies with enhanced activity against Fab and Fc fragments of IgG. In surviving mice, the level of anti-DNA antibodies, particularly those of IgG1 isotype, were significantly decreased. Flow cytometric analysis of various T cell subsets showed that the number of cells expressing gamma delta T cell receptor (TcR) antigens which did not vary with age was not modified after P-IgG or P-IgM treatment. In contrast, the number of T cells expressing V beta 8.1,2,V beta 10 and V beta 14 TcR antigens, which increased with age, were significantly reduced. Taken together, these results indicate that parasite infection of mice induces the synthesis of populations of IgM and IgG natural autoantibodies with immunoregulatory properties and that these antibodies attempt, at least transitorily, to rescue a natural autoantibody network that is deficient in B/W mice.
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PMID:Beneficial effect of polyclonal immunoglobulins from malaria-infected BALB/c mice on the lupus-like syndrome of (NZB x NZW)F1 mice. 802 May 74

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

Testicular autoimmune disease (autoimmune orchitis) develops in mice immunized with testis antigen in adjuvant, occurs spontaneously in dogs, mink, and horses, and is a potential cause of human infertility. This is the first study to investigate autoimmune orchitis using monoclonal T cells. Despite the use of crude tissue antigens, 100% of the T cell lines/clones transferred autoimmune disease of the male gonad to normal syngeneic mice, with pathology that affected the testis, the epididymis and/or the vas deferens. Thus orchitogenic peptides are likely of restricted number and/or of dominant immunogenicity. Upon transfer to normal mice, the mildest and earliest pathology elicited by the cloned T cells invariably occurred in a specific region, the testicular straight tubules. Although testis antigen-derived T cell clones responded preferentially to testis antigen, and sperm antigen-derived clones responded more to sperm antigens, each of the 16 clones respond to both antigens. Thus common orchitogenic antigens exist in these germ cell populations though their quantity may differ in distribution. All orchitogenic T cell lines and clones expressed CD4 and the alpha beta T cell receptor; and when activated, they produced interleukin 2, interferon gamma, and tumor necrosis factor (TNF), but not interleukin 4. This cytokine profile characterizes the Th1 CD4+ T cell subset, known to be responsible for the delayed type immunological reaction. Importantly, since disease transfer was significantly and reproducibly attenuated when recipients were injected with neutralizing antibody to TNF, but not neutralizing antibody to interferon gamma, TNF has been defined as a cytokine important in the pathogenesis of this autoimmune disease.
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PMID:Experimental autoimmune orchitis induced by testis and sperm antigen-specific T cell clones: an important pathogenic cytokine is tumor necrosis factor. 810 48

Previous studies have shown that murine anti-CD4 monoclonal antibody, cross-linked by rabbit anti-mouse immunoglobulin, could mediate apoptosis of murine CD4+ lymphocytes when they were stimulated by T cell receptor antibody. In this study, we have shown that the murine anti-CD4 monoclonal antibody, OKT4, can induce apoptosis in human CD4+ T cells stimulated by the recall antigen tuberculin purified protein derivative (PPD) only when cross-linked by rabbit anti-mouse immunoglobulin. The chimeric anti-CD4 monoclonal antibody, cM-T412 whose Fc fragment is human, was able to cause apoptosis without cross-linking by a second antibody. Similarly, abolition of PPD-induced proliferation of peripheral blood mononuclear cells by cM-T412 did not require cross-linking with rabbit anti-human immunoglobulin. Inhibition of proliferation by cM-T412 could be reduced by pre-treating monocytes with heat-aggregated human IgG. This suggested that monocyte Fc gamma receptors might be cross-linking the human Fc of cM-T412. Propidium iodide staining together with immunofluorescence showed that the apoptotic cells were indeed CD4+ lymphocytes. It is proposed that during treatment with cM-T412 in autoimmune disease such as rheumatoid arthritis, cM-T412-coated CD4 T cells, when they are subsequently stimulated by the unknown arthritogenic antigen, may undergo apoptotic cell death through cross-linking of cM-T412 on Fc gamma receptor-positive cells within the joint.
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PMID:Chimaeric anti-CD4 monoclonal antibody cross-linked by monocyte Fc gamma receptor mediates apoptosis of human CD4 lymphocytes. 810 99

Recent advancement in immunology has revealed that autoimmune diseases occur when T lymphocytes become activated on recognizing a self-antigen linked to the autologous class II molecule of the major histocompatibility complex (MHC). The resulting complex of antigen, MHC, and T cell receptor could be a target for treatment of autoimmune disease. This approach is now being studied in animal models. Experimental autoimmune uveoretinitis is a T cell mediated autoimmune disease directed against retinal proteins and has been studied as a model for human uveitis. In Lewis rats, uveitogenic peptides and uveitogenic T cell receptor families have been detected. It is a first step toward developing specific immunotherapy. This paper describes a general outline of the steps of T cell activation and ways of suppression of autoimmune diseases by the modulation of these steps, especially in experimental autoimmune uveoretinitis.
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PMID:[New approaches to the regulation of autoimmune disease]. 810 55

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

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease that can be induced in laboratory animals by immunization with the major myelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP). We analyzed the role of the T cell receptor (TCR) repertoire in susceptibility to EAE induced by these two autoantigens. Autoreactive T cells induced after immunization with MBP use a limited set of TCR. In contrast, we demonstrate that T cell clones that recognize the encephalitogenic PLP epitope (PLP 139-151) use diverse TCR genes. When the TCR repertoire is limited by introduction of a novel rearranged TCR V beta 8.2 chain in transgenic SJL mice, EAE could be induced in the transgenic mice by immunization with the encephalitogenic epitopes of PLP, but not with the encephalitogenic epitope of MBP. Thus, skewing the TCR repertoire affects the susceptibility to EAE by immunization with MBP but not with PLP. These data demonstrate the biological consequences of the usage of a more diverse T cell repertoire in the development of an autoimmune disease.
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PMID:T cell receptor (TCR) usage determines disease susceptibility in experimental autoimmune encephalomyelitis: studies with TCR V beta 8.2 transgenic mice. 816 44

We have previously reported 2 cases of healthy men showing in vivo monoclonal expansion of mature CD4- CD8- alpha beta T cells. In the present study, an additional 3 adults were found to exhibit such an expansion, among a total 464 adult donors studied. These 5 individuals were otherwise physiologically normal, with no history of severe illness and autoimmune disease at the time of examination. To investigate the mechanisms of the clonal expansion, further characterization of the clonal cells was attempted. No apparent preference for usage of the T cell receptor beta chain variable region was observed in the clonal T cells. These clonal T cells showed lectin-dependent or redirected antibody-dependent cell-mediated cytotoxicities, whereas they could not lyse autologous lymphoblastoid cell lines. Failure of Fas antigen expression was not observed for any of these clones. These results suggest that clonal expansion of CD4- CD8- alpha beta T cells frequently occurs in the periphery without any T cell abnormalities.
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PMID:Frequent occurrence of in vivo clonal expansion of CD4- CD8- T cells bearing T cell receptor alpha beta chains in adult humans. 822 48

The lpr gene induces in mice, accumulation of large numbers of CD4-CD8- (double negative [DN]) T lymphocytes which bear adhesion molecules not characteristic of normal resting T cells. These cells fail to acquire interleukin 2 (IL-2) receptors, produce IL-2, and proliferate when activated with mitogens or monoclonal antibodies (mAbs) against the T cell receptor (TCR). Because of these poor functions in vitro, the nature and significance of DN T cells in the autoimmune disease process is not clear. In the current study, we describe a surprising finding that mAbs against CD3-TCR-alpha/beta complex can strongly trigger the lytic activity of the DN T cells to induce redirected lysis of Fc receptor-positive targets. Similar redirected lysis was also inducible using mAbs against CD44 and gp90MEL-14, molecules involved in the binding of lymphocytes to endothelial cells. The spontaneous cytotoxic potential of the DN T cells was further corroborated by demonstrating that the lpr DN T cells constitutively transcribed perforin gene but failed to express granzyme A. The current study suggests that DN T cells are capable of mediating lysis of autologous cells bearing the specific ligands for adhesion molecules involved in the signaling of cytotoxicity. These findings provide a novel insight into the functional significance of DN T cells in lpr mice and their potential role in the pathogenesis of autoimmune disease.
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PMID:Double-negative T cells from MRL-lpr/lpr mice mediate cytolytic activity when triggered through adhesion molecules and constitutively express perforin gene. 824 94

Collagen type II-induced arthritis (CIA) is generated in susceptible rodent strains by intradermal injections of homologous or heterologous native type II collagen in complete Freund's adjuvant. Symptoms of CIA are analogous to those of the human autoimmune disease, rheumatoid arthritis. CIA is a model system for T cell-mediated autoimmune disease. To study the T cell receptor (TCR) repertoire of bovine type II-specific T cells that may be involved in the pathogenesis of CIA in DBA/1Lac.J (H-2q) mice, 13 clonally distinct T cell hybridomas specific for bovine type II collagen have been established and the alpha and beta chains of their TCRs have been analyzed. These T cell hybridomas recognize epitopes that are shared by type II collagens from distinct species and not by type I collagens, and exhibit a highly restricted TCR-alpha/beta repertoire. The alpha chains of the TCRs employ three V alpha gene subfamilies (V alpha 11, V alpha 8, and V alpha 22) and four J alpha gene segments (J alpha 42, J alpha 24, J alpha 37, and J alpha 32). The V alpha 22 is a newly identified subfamily consisting of approximately four to six members, and exhibits a high degree of polymorphism among four mouse strains of distinct V alpha haplotypes. In addition, the beta chains of the TCRs employ three V beta gene subfamilies (V beta 8, V beta 1, and V beta 6), however the V beta 8.2 gene segment is preferentially utilized (58.3%). In contrast, the J beta gene segment usage is more heterogeneous. On the basis of the highly limited TCR-alpha/beta repertoire of the TCRs of the panel of bovine type II-specific T cell hybrid clones, a significant reduction (60%) of the incidence of arthritis in DBA/1Lac.J mice is accomplished by the use of anti-V beta 8.2 antibody therapy.
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PMID:Characterization of the T cell receptor repertoire causing collagen arthritis in mice. 838 Nov 55


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