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Query: UMLS:C0003864 (arthritis)
 69,039 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Collagen induced arthritis is an experimental animal model of inflammatory polyarthropathy that has many features of human rheumatoid arthritis. Type II collagen is the major matrix protein of hyaline cartilage and is a sequestered protein which can be presented as an autoantigen under certain conditions. To induce CIA, type II collagen is injected intradermally with complete Freund's adjuvant. Susceptibility to CIA is dependent on the presence of the trimolecular complex: 1) the arthritogenic epitope on the type II collagen; 2) a class II MHC molecule on the accessory cell presenting the arthritogenic epitope; and 3) T cells expressing specific V beta chains in their TCRs. Complement and other non-MHC background genes also may play a role in susceptibility to CIA. Both cell mediated and humoral immunity are involved in the pathogenesis of CIA. To date immunotherapies that have modulated CIA include use of anti-class Ii antibodies, anti-lymphokines, and monoclonal antibodies directed against specific cellular markers. All of these therapies are able to modulate disease to some extent but lack the specificity and efficacy to make them practical for widespread use in human disease. Most promising, is the use of monoclonal antibodies directed against specific V beta TCR subsets. This is potentially a very specific and effective therapy because it will affect only the cells involved in disease while leaving the host otherwise immunocompetent. Therapies on the horizon include the use of synthetic peptides with sequences homologous to various regions on the TCR, immunotoxins, and superantigens to modulate the immune response and ameliorate disease.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunogenetics of collagen induced arthritis in mice: a model for human polyarthritis. 128 54

We have used PCR to study the expression of T-cell antigen receptor beta RNA containing particular variable region (V) elements from transcripts directly in the cells isolated from joints and lymph nodes of B10.Q mice (H-2q) immunized with chicken type II collagen. Our data show that the T cells present in arthritic joints expressed only a few V beta transcripts--V beta 2, -6, -7, -8.2, -9, -10, and -15. V beta 6 and -8.2 were expressed predominantly (six out of seven animals) while others were expressed at a relatively low level in different animals. In lymph node cells, transcripts for V beta 6, -8.2, and -9 were detected in four out of seven animals. The data indicate that in collagen-induced arthritis there is a restrictive usage of TCR V beta elements and that V beta 6 and -8.2 are probably used preferentially.
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PMID:Restricted heterogeneity in T-cell antigen receptor V beta gene usage in the lymph nodes and arthritic joints of mice. 131 Oct 91

The effects of treatment with a monoclonal antibody (R73 mAb) against T cell receptor alpha/beta (TCR-alpha/beta) on both established adjuvant arthritis (EAA) and established collagen-induced arthritis (ECIA) in rats have been investigated. Rats were treated with R73 mAb when arthritis reached a peak. Treatment with the anti-TCR-alpha/beta mAb markedly suppressed EAA, whereas ECIA was not affected by the mAb treatment. Histologically, R73 mAb-treated rats with EAA showed mild hyperplasia of synovial tissues, sparse infiltration of inflammatory cells, and minimal erosion of cartilage, whereas arthritic rats treated with PBS and an irrelevant control mAb against Giardia had marked hyperplasia of synovium with pannus, massive inflammatory cell infiltrate, and severe destruction of cartilage and subchondral bone. R73 mAb-treated rats with ECIA exhibited pronounced formation of pannus containing many inflammatory cells and marked cartilage and subchondral damage similar to those in arthritic rats that received the control treatments. Treatment with R73 mAb depleted markedly alpha/beta+ T cells in both peripheral blood and synovial tissues of rats with EAA and ECIA. R73 mAb treatment was associated with marked reduction in arthritogen-specific delayed-type hypersensitivity responses in both EAA and ECIA. The titers of antibodies against type II collagen produced in rats with ECIA were not affected by the mAb. Thus, alpha/beta+ T cells appear to have a central role in EAA, but not in chronic ECIA.
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PMID:Depletion of alpha/beta T cells by a monoclonal antibody against the alpha/beta T cell receptor suppresses established adjuvant arthritis, but not established collagen-induced arthritis in rats. 137 48

SWR/J transgenic (tg) mice were generated expressing the TCR beta chain derived from an anticollagen type II (CII) arthritogenic T cell clone. The SWR/J strain was selected because it is resistant to collagen-induced arthritis (CIA) and lacks the V beta gene segment used by the T cell clone. Expression of the tg beta chain on all thymocytes and peripheral lymph node T cells led to a more efficient anti-CII immune response, but did not confer CIA susceptibility to SWR/J mice. Nevertheless, this tg beta chain enhanced predisposition to CIA as (DBA/1 x SWR) F1 beta tg mice were more susceptible than normal F1 littermates. Our results demonstrate that the expression of the tg beta chain contributes to CIA susceptibility, but by itself it is not sufficient to overcome CIA resistance in the SWR/J strain.
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PMID:Expression of a transgenic T cell receptor beta chain enhances collagen-induced arthritis. 138 71

T lymphocyte responses to heterologous or self 65-kD heat shock protein (hsp) have been implicated in the pathogenesis of various forms of arthritis. To delineate the relationship of 65-kD hsp to different synovial fluid (SF) T cell subsets, we stimulated synovial fluid (SFMC) and peripheral blood mononuclear cells (PBMC) from patients with different inflammatory rheumatic diseases and from healthy controls with human or mycobacterial 65-kD hsp, tetanus toxoid (TT), heat-killed or live Yersinia enterocolitica. Phenotyping of the resulting T cell lines revealed an increase of up to 97% TCR-gamma delta+ lymphocytes in the 65-kD hsp-stimulated SF-derived lines. This expansion of TCR-gamma delta+ cells was less pronounced with cultures of PBMC. A preferential expansion of TCR-gamma delta+ cells was also shown after SFMC stimulation with live, but not with heat-killed Yersinia or with TT. We conclude that a common mechanism is involved in the selective expansion of TCR-gamma delta+ lymphocytes upon SFMC infection with live Yersinia or upon contact with 65-kD hsp. Out of a panel of TCR-gamma delta+ T lymphocyte clones (TLC) derived from a human 65-kD hsp-stimulated line, only a minority of TLC proliferated weakly upon restimulation with this antigen in the presence of autologous monocytes, whereas TCR-alpha beta+ TLC responded vigorously to the human 65-kD hsp and in some cases also cross-recognized the mycobacterial hsp homologue and/or heat-killed Yersinia. This implies that additional factors or cells may be present in the milieu of SFMC cultures that propagate the expansion of TCR-gamma delta+ cells in response to 65-kD hsp or live bacteria.
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PMID:Stimulation of synovial fluid mononuclear cells with the human 65-kD heat shock protein or with live enterobacteria leads to preferential expansion of TCR-gamma delta+ lymphocytes. 138 95

HLA-DR, HLA-DQ, and T cell receptor beta (TCR beta) chain gene polymorphisms were investigated in 43 patients with rheumatoid arthritis (RA), in 10 patients with Felty's syndrome (FS), and in 5 RA multicase families. RA was found to be strongly associated with a DRB1 gene sequence motif present in DR1, DR4-Dw4, and DR4-Dw14 alleles. Ninety-three percent of RA patients were positive for at least 1 of these alleles, providing strong support for the "shared epitope hypothesis." The frequency distribution of this sequence motif suggests a dominant mode of inheritance. All 10 FS patients were DR4-Dw4 positive. Different DR-DQ associations among DR4 positive RA and FS patients indicate heterogeneity in the genetic susceptibility to these 2 disease entities. Furthermore, analyses of TCR V beta 8, V beta 11, and C beta gene polymorphisms did not support the notion of an influence of TCR beta germline allotypes on RA susceptibility.
Arthritis Rheum 1991 Nov
PMID:Association of rheumatoid arthritis with a dominant DR1/Dw4/Dw14 sequence motif, but not with T cell receptor beta chain gene alleles or haplotypes. 162 29

Intrathymic tolerance results in elimination of T cells bearing self-reactive TCR V beta regions in mice expressing certain combinations of I-E and minor lymphocyte stimulatory (Mls) phenotypes. To determine if autoimmune strains of mice have a defect in intrathymic deletion of self-reactive TCR V beta regions, expression of V beta 3, V beta 6, V beta 8.1, and V beta 11 were examined in lpr/lpr and +/+ strains of mice; MRL/MpJ(H-2K, I-E+, Mlsb,), C57BL/6J(H-2b, I-E-, Mlsb,), C3H/HeJ(H-2k, I-E+, Mlsc), AKR/J(H-2k, I-E+, Mlsa); and in autoimmune NZB/N(H-2d, I-E+, Mlsa) and BXSB(H-2b, I-E-, Mlsb) mice. The results suggest that, during intrathymic development, self-reactive T cells are deleted in autoimmune strains of mice as found in normal control strains of mice. However, the TCR V beta repertoire is skewed in autoimmune strains compared to normal strains of mice. For example, MRL-lpr/lpr mice, but not other lpr/lpr strains, had increased expression of V beta 6 relative to expression in control MRL(-)+/+ mice, which is associated with collagen-induced arthritis. These data are consistent with a model of normal affinity for negative selection of self-reactive T cells in the thymus of autoimmune strains of mice followed by expansion of autoreactive T cell clones in the peripheral lymphoid organs. The peripheral lymphoid organs of lpr/lpr mice contain an expanded population of abnormal CD4-, CD8-, 6B2+ T cells. Elimination of self-reactive peripheral T cells suggests that these abnormal cells are derived from a CD4+ subpopulation in the thymus. Flow cytometry analysis of peripheral lymph node T cells from MRL-lpr/lpr mice reveal three populations of CD4+ T cells expressing low, intermediate and high intensity of B220 (6B2). This supports the hypothesis that in lpr/lpr mice, self-reactive CD4+ T cells are eliminated in the thymus, and that these cells lose expression of CD4 and acquire expression of 6B2 in the periphery.
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PMID:Altered expression of self-reactive T cell receptor V beta regions in autoimmune mice. 169 Feb 37

Rats treated with an mAb (R73) against the TCR-alpha beta failed to develop chronic persistent arthritis after injection of streptococcal cell walls. Histologically, R73 mAb-treated rats had mild hyperplasia of synovial lining cells and minimal destruction of cartilage. In contrast, control-treated animals developed marked pannus formation, with pronounced infiltration of mononuclear cells and severe destruction of cartilage and subchondral bone. The preventive effect of R73 mAb on streptococcal cell wall-induced arthritis was associated with the marked depletion of alpha beta + T cells by R73 mAb. These results indicate that T cells play a crucial role in chronic erosive streptococcal cell wall-induced arthritis.
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PMID:Prevention of chronic erosive streptococcal cell wall-induced arthritis in rats by treatment with a monoclonal antibody against the T cell antigen receptor alpha beta. 182 61

The anti-rat alpha/beta-TCR, MAb-R73 has been investigated as to its disease modifying activity on adjuvant arthritis (AA), on experimental allergic encephalomyelitis (EAE) and on a local graft versus host (GvH) reaction (popliteal lymph nodes = PLN) in Lewis or Brown-Norway rats. R73 was able to prevent the onset of the AA and even if therapy started after the establishment of AA the MAb was still able to reduce the degree of chronic inflammation and arrest its progress. Intravenous MAb-R73 application also reduced the signs of EAE and prevented mortality. This was even seen when the substance was given after the outbreak of the clinical symptoms or when the F(ab)2 fragment of this MAb was used. Also in the model of local GvH reaction R73 acted therapeutically and lowered the PLN weights.
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PMID:Inhibitory effects of the anti-rat T-cell receptor (TCR) monoclonal antibody (MAb) R73 on various experimental autoimmune diseases. 183 95

A monoclonal antibody (MAb) to the alpha/beta T cell receptor (TCR alpha/beta), R73 MAb, completely blocked the induction of collagen-induced arthritis (CIA) in rats when the MAb was administered at the time of immunization with type II collagen. When administered after CIA had begun, the progression of the arthritis was suppressed significantly by R73 MAb treatment. The preventive and suppressive effects of R73 MAb on CIA were associated with the depletion of peripheral blood alpha/beta-positive T cells. These results indicate that alpha/beta-positive T cells play a role in the progression of existing CIA as well as in its induction.
Arthritis Rheum 1991 Aug
PMID:Treatment of collagen-induced arthritis in rats with a monoclonal antibody against the alpha/beta T cell antigen receptor. 185 78


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