Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Mouse strains B10, B10.RIII, RIIIS/J and the F1 and backcross progeny arising from them were tested for susceptibility to porcine type II collagen-induced arthritis (PII-CIA). The clinically severe arthritis of rapid onset that is characteristic of PII-immunized B10.RIII mice developed predominantly in hybrid offspring that had inherited at least one copy of wild type T cell receptor (TCR) genes (V beta b genotype) from the B10 or B10.RIII parent. The results indicate that, in the development of PII-CIA, mice expressing the H-2r/r haplotype preferentially utilize TCR V beta genes that are normally encoded within the TCR V beta genomic deletion region of RIIIS mice (V beta c). After aggressive immunization with PII, the use of alternative TCR V beta genes, encoded outside of the RIIIS deletion region, produced a high IgG antibody response that was cross-reactive with mouse type II collagen (MII) and equivalent to that of B10.RIII mice, but only a very mild, late onset arthritis of 56% (27/48) incidence in RIIIS male mice and 28% (10/35) incidence in RIIIS female mice. In comparison, B10.RIII mice routinely developed early onset of PII-CIA of significantly higher incidence (100%; p < 0.005) and four-fold greater severity, even after milder immunization protocols. The data are compatible with the proposal that the clinically weak CIA response of RIIIs mice may be primarily antibody driven while the severe CIA of B10.RIII mice reflects the added inflammatory effects of collagen-reactive effector-T cells in the joint.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:T-cell receptors and collagen induced arthritis in H-2r mice. 832 59

Counteracting the effect of autoimmunity can be achieved by elimination or inactivation of autoreactive T cells. We have focused on two approaches targeting on autoaggressive T cells in the model of collagen-induced arthritis (CIA) in mice. First, type II collagen (CII) primed DBA/1 mice were treated with various monoclonal antibodies (mAb) specific for the beta chains of the T cell receptor (TCR) using a protocol resulting in a long-term elimination of the target T cells. Indeed, CIA could be suppressed by injection of anti-V beta 8.1, 2 mAb and down-regulated by that of anti-V beta 2 and/or anti-V beta 5, presumably by deleting pathogenic T cell clones. In contrast, treatment with either anti-V beta 6 or anti-V beta 11 mAb did not alter CIA. Second, we generated CII-specific T cell hybrid clones that recognize the antigenic peptides in association with Kq and IA(q) molecules respectively for CD8+ and CD4+ cells. Vaccination with the irradiated hybrid clones, 3 weeks prior to immunization, was effective in preventing the development of arthritis. Furthermore, this suppression was antigen and disease specific. Most importantly, one CD8+ clone could reverse the ongoing disease. These new therapeutic approaches derived from animal models may offer a hope of more selective interventions for the treatment of human autoimmune diseases.
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PMID:T cell-targeted immunotherapy in murine collagen-induced arthritis. 835 99

Up to now the data regarding T cell receptor V-gene usage by juvenile chronic arthritis synovial T lymphocytes has been conflicting. Thus, some studies claim that locally in the diseased joint there is an oligoclonal expansion of T cells with restricted T cell receptor variable region gene usage while others have found V-gene usage in the joint compatible with a polyclonal expansion of the T cells.
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PMID:T cell receptor variable region gene usage in juvenile chronic arthritis. 835 7

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

Eight HLA B27-restricted influenza A virus nucleoprotein 383-391-specific cytotoxic T lymphocyte (CTL) clones were obtained from three unrelated donors following natural infection. T cell receptor (TcR) usage was studied using the "anchored" polymerase chain reaction. TcR alpha-chain usage was restricted with three predominant V alpha (V alpha 12.1, 14.1, 22) and two predominant J alpha segments. beta-chain variable-region usage was also conserved, with V beta 7 being used by five clones despite contributing less than 2% of peripheral blood lymphocyte V beta sequences of one individual studied. The TcR beta-chain junctional region was highly conserved even between CTL clones from unrelated individuals, with a negatively charged amino acid, contributed to by N-region addition, encoded at position 97 in all but two clones. This study shows that peptide-specific HLA B27-restricted CTL following influenza virus infection use very similar TcR and, when considered with previous studies, suggests a pattern of TcR conservation for major histocompatibility complex class I-restricted responses. No difference in TcR usage was detected between one healthy donor and two with HLA B27-associated arthritis.
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PMID:Conservation of T cell receptor usage by HLA B27-restricted influenza-specific cytotoxic T lymphocytes suggests a general pattern for antigen-specific major histocompatibility complex class I-restricted responses. 839 85

Collagen induced arthritis (CIA) is an animal model of inflammatory polyarthritis. Immunotherapy with the monoclonal antibody F23.1, which deletes V beta 8 bearing T cells, significantly decreased the incidence of CIA in mice. Treatment with the monoclonal antibody 466B5, to delete V beta 6 bearing T cells in combination with F23.1 was no more effective than F23.1 alone and the CIA incidence in 466B5 treated animals was not significantly different from controls. Thus, the V beta 8 family of T cell receptor is expressed on self-reactive T cells in the CIA model of B10.RIII mice injected with porcine type II collagen.
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PMID:Prevention of collagen induced arthritis in mice by deletion of T cell receptor V beta 8 bearing T cells with monoclonal antibodies. 842 55

Superantigens include bacterial products (mainly of streptococci and staphylococci) that stimulate T cells to proliferate nonspecifically through interaction with class II major histocompatibility complex products on antigen-presenting cells and then with variable regions on the beta chain of the T cell receptor complex. They include pyrogenic toxins (streptococcal scarlet fever toxins of serotypes A, B, and C, toxic shock syndrome toxin 1, and staphylococcal enterotoxin serotypes A, B, Cn, D, E, and G), streptococcal M protein, staphylococcal exfoliative toxin, and recently identified pyrogenic toxins made by groups B, C, F, and G streptococci and Streptococcus sanguis. Pyrogenic toxin superantigens cause acute toxic shock syndrome and are associated with toxic shock-like syndromes. Superantigens cause symptoms via release of immune cytokines. These proteins should be considered potential causes of illnesses such as rheumatic fever, arthritis, Kawasaki syndrome, atopic dermatitis, and guttate psoriasis because of their potent immune system-altering capacity.
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PMID:Role of superantigens in human disease. 848 72

Synovial tissue is rarely available from patients with early synovitis, with the exception of synovial biopsies. However, T cell populations early in the development of synovitis may be enriched in antigen-specific cells and critical to disease pathogenesis. To investigate the T cell repertoire in early synovitis, we utilized a PCR protocol for detection of T cell receptor (TCR) transcripts present in small amounts of synovial tissue. To expand the substrate for PCR, preamplification of cDNA was performed with a 3' constant region primer plus either a mixture of variable region primers or random hexanucleotides. Utilizing this method improved the sensitivity of detection. This technique is applied here to the analysis of TCR transcripts in synovial biopsies from individuals with early rheumatoid arthritis (RA) and non-RA synovitis. TCR alpha-chain transcripts were detectable in 5/5 RA and 4/4 non-RA specimens evaluated, with beta-chain transcripts detected in 4/5 early RA and 4/4 non-RA specimens evaluated. Confirmation of transcripts by sequencing of cloned PCR products verified the specificity of amplification. The most frequently expressed TCR V region families in early RA synovitis were V alpha 11, V alpha 14, V alpha 28, V beta 7, V beta 9 and V beta 17. Several of these V regions have previously been implicated in studies of chronic RA synovitis. J alpha and J beta region usage was similar to that seen in chronic RA, and conserved N region motifs were apparent. We conclude that it is possible to detect TCR transcripts in small synovial biopsies from individuals with early arthritis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Detection of T cell receptors in early rheumatoid arthritis synovial tissue. 855 98

The genetic basis of complex (auto)immune diseases has been studied for an ovine nematode infection, human rheumatoid arthritis (RA), early onset pauciarticular arthritis (EOPA) and multiple sclerosis (MS). Immunoprinting combines the powerful simplicity of polymerase chain reaction (PCR)-based amplification of discrete, highly informative microsatellite loci with the principle of genetic associations. This approach has allowed us to define novel genetic risk factors in adult RA patient categories whereas EOPA forms in juveniles display other prominent genetic contributions. Differentially regulated tumor necrosis factor (TNF) expression may lead to a better understanding of the causal pathogenesis of EOPA while T cell receptor (TCR) gene polymorphisms appear crucial for RA manifestations in certain patient groups. Statistically significant marker associations have still to be defined for MS in larger panels of patient and control cohorts. The clinical course of the disease will probably have to be taken into account when associations with lymphokine levels are evaluated. In essence a convoluted myriad of negative and a few positive disease association data have been generated efficiently by immunoprinting. As expected, the interrelationships are truly complicated between the polymorphic genetic instances predisposing to autoimmune disease. Nevertheless, risk factors may be defined on an individualized basis by indirect gene diagnosis revealing predispositions and providing a more solid basis for differential diagnosis and treatment.
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PMID:Immunoprinting reveals different genetic bases for (auto)immuno diseases. 858 58

There is considerable evidence to implicate T cells in the pathogenesis of rheumatoid arthritis (RA). They initiate and sustain inflammation and therefore are attractive targets for immunotherapy. Several strategies targeting T cells have been tried in RA. The use of monoclonal antibodies to deplete T cells have been used extensively but with little success. Studies have shown that T cell depleting antibodies produce profound peripheral blood lymphopenia but they are less effective in depleting lymphocytes in the joint. Since clinical efficacy is likely to depend on depleting almost all synovial lymphocytes, high doses of monoclonal antibodies would have to be given. However, the invariably severe peripheral blood lymphopenia induced by such a regimen is likely to result in profound immunosuppression. Therefore, this strategy has been abandoned and recent attempts have been made to induce tolerance in RA. In animal models of RA, treatment with high dose non-depleting anti-CD4 monoclonal antibody protects them from arthritis induced by injection of streptococcal cell wall. In addition, it leads to a state of anergy which protects the animals from arthritis induction without further treatment with anti-CD4 monoclonal antibody. This is currently being used in clinical trials of RA. Other tolerance inducing treatment strategies include T cell or T cell receptor vaccination and oral tolerance. The former is particularly difficult since the rheumatoid arthritogenic antigen and the pathogenic T cell remain unknown. The latter has shown promise in placebo controlled trials although the ideal dosage remains unknown. The mechanism of action of oral tolerance involves either immunosuppressive T cell cytokines, T cell anergy or depletion.
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PMID:Innovative treatment approaches for rheumatoid arthritis. T-cell regulation. 859 47


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