UMLS:C0003864 - FACTA Search

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

Reactional states in leprosy are produced by different immunologic mechanisms and are responsible for a major component of tissue damage of the disease. Reversal reactions exhibit increased CD4 T cell infiltration in lesions and augmented cell-mediated immune reactivity to Ag of Mycobacterium leprae that can rapidly produce nerve damage. Erythema nodosum leprosum (ENL) reactions also have CD4 T cell infiltration but appear to be associated with the formation of immune complexes that are responsible for panniculitis, arthritis, vasculitis, and nerve injury. Because these reactional states may serve as paradigms for other types of human immunologically mediated tissue damage, this study sought to characterize the dynamic changes in cytokines associated with these reactions. Expression of cytokine mRNA in lesions of leprosy reactional states were measured by PCR. In reversal reactions, IL-1 beta, TNF-alpha, IL-2, and IFN-gamma mRNA were prominent and found to increase during the reaction, concomitant with decreases in expression of mRNA for IL-4, IL-5, and IL-10. In ENL, selective increases in the expression of IL-6, IL-8, and IL-10 mRNA was observed, with persistent expression of IL-4 and IL-5 mRNA. Reversal reactions represent naturally occurring delayed-type hypersensitivity reactions that favor macrophage activation and protective immunity, but which can engender concomitant cell injury. In contrast, ENL lesions represent immediate-type hypersensitivity reactions reflecting the selective stimulation of cytokines that attract neutrophils, stimulate antibody production, and down-regulate macrophage activation. The analysis of cytokine dynamics within different inflammatory responses can provide insights into immune mechanisms of tissue damage, and provide a useful framework for developing strategies for therapeutic intervention.
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PMID:Cytokine patterns of immunologically mediated tissue damage. 150 Jul 26

The profile of lymphokines secreted by 14 T cell clones and 24 T cell lines reactive with Yersinia Ag isolated from the synovial fluid cells of two HLA-B27+ patients with Yersinia-triggered reactive arthritis was characterized. In response to Ag-specific or -nonspecific stimulation, all of the Yersinia-reactive T cell clones and lines had a pattern of lymphokine secretion resembling that of murine (Th1) cells. A total of 50% of T cell lines and clones randomly isolated from a reactive arthritis patient, without prior in vitro stimulation with Yersinia Ag, also exhibited a Th1-like profile of cytokine secretion upon nonspecific activation. This indicates that the selective expansion of this subset of T cells had already occurred in vivo. The possibility that the predominance of Th1-like T cells was an artefact generated by the T cell cloning procedure was excluded; 50% of the randomly isolated T cell clones and lines produced IL-4, IL-5, or both cytokines upon nonspecific activation. These results indicate that Yersinia Ag selectively activate a Th1-like subset of T cells in patients with Yersinia-triggered reactive arthritis. Accumulation of such cells in the synovial tissue of patients with reactive arthritis may play a key role in the pathogenesis of this disease.
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PMID:Yersinia enterocolitica activates a T helper type 1-like T cell subset in reactive arthritis. 153 51

CD4+ T helper cells play a critical role in the chronicity of collagen-induced arthritis (CIA) in mice. The present results focus on the involvement of Th1 and Th2 subsets at the initial stage of the experimental disease in two lines of mice selected for high antibody production: HI that is susceptible, and HII that is resistant to CIA. Both lines are known to be H-2q, display an identical full set of V-beta genes, and mount similar antibody responses to both heterologous and autologous CII. The kinetic analysis of local T cell and anti-bovine CII antibody responses was followed by Elispot assays, the production of interferon-gamma (IFN-gamma) and IgG2a being considered indicative of a Th1 profile, and interleukin-5 (IL-5) as well as IgG1-IgE, of a Th2 profile. The number of IL-5 Elispots is constantly higher in susceptible than in resistant mice. The IFN-gamma production is rather low in HI compared to HII, and besides, preferential help is observed for the Th2-dependent IgG1-IgE isotype-producing B cells in HI, while a switch-over toward IgG2a anti-CII isotype is found in HII. These results suggest that a Th1 preeminence at the onset of the anti-CII response is decisive in the resistance to CIA.
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PMID:T helper subset involvement in two high antibody responder lines of mice (Biozzi mice): HI (susceptible) and HII (resistant) to collagen-induced arthritis. 784 23

Immunization of DBA/1 mice with bovine type II collagen (CII) in complete Freund's adjuvant (CFA) leads to collagen-induced arthritis as evidenced by joint inflammation. In this study, reverse transcription-polymerase chain reaction (RT-PCR) was used to demonstrate the activation of genes encoding for IL-2, IFN-gamma, and IL-10 in the lymph nodes from both CII-immunized and control CFA-immunized DBA/1 mice, at Days 10, 40, and 70 after immunization, in the absence of any IL-5 or IL-13 transcription. By quantitative RT-PCR, the levels of IFN-gamma mRNA in response to CII could not be quantitatively differentiated from the IFN-gamma transcribed in response to CFA alone. In the joints of CII-immunized mice, IL-1beta and IL-10 mRNA were found in the absence of IL-5 or IFN-gamma. Synovial IL-1beta and IL-10 were expressed most strongly at the time of clinical symptoms, 40 days after immunization. Together, these findings suggest that immunization with CII in CFA induces a type 1 response against the adjuvant, giving a cytokine environment which influences the T cells responding to CII to become type 1 T cells. This is manifested here by the appearance of gene activation in synovial tissue of collagen-immunized mice, but not in adjuvant-immunized control animals.
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PMID:Collagen-induced arthritis in DBA/1 mice: cytokine gene activation following immunization with type II collagen. 891 86

The kinetics of cytokine production in arthritic limbs of mice with CIA was determined by using modified immunohistochemical techniques. Tissue cryostat sections of undecalcified whole paws were analysed for the presence of tumour necrosis factor-alpha (TNF-alpha), IL-6, IL-2, IL-4, IL-5 interferon-gamma (IFN-gamma), transforming growth factor-beta 2 (TGF-beta2) and TGF-beta3. Locally produced TNF-alpha, IL-6 and TGF-beta2 were observed within the lining layer, sublining and pannus at all stages of disease. The staining of TNF-alpha was particularly intense at the cartilage-pannus junction. In contrast to the monokines, IFN-gamma and TGF-beta3 were only expressed in scattered cells within the deeper layers of the synovia. Interestingly, IFN-gamma was not present in the late phase of CIA, despite the continued presence of TNF-alpha and IL-6 in the pannus. Production of IL-2, IL-4 or IL-5 was not detected in any joint. The observed pattern of a relative paucity of T cell-derived cytokines and an abundance of monokines during the late phase of T cell-dependent CIA indicates that the synovial cytokine pattern previously described in rheumatoid arthritis (RA) is fully compatible with a pathogenic role of T cells. The temporal as well as spatial dissociation between expression of T cell-derived cytokines and monokines indicates that T cell-independent mechanisms may also be of importance in the triggering of monokine production during arthritis.
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PMID:Cytokine production in synovial tissue of mice with collagen-induced arthritis (CIA). 906 22

Over the past decade, the central role of T cells in the process of collagen-induced arthritis (CIA) has been extensively documented. The inflammatory features of CIA and its successful modulation after treatment in vivo with Th2 lymphokines, known to down-regulate proinflammatory cytokines, classify CIA as a Th1-mediated disease. However, no direct evidence for the presence of the different T helper subsets has been obtained. To identify the collagen-specific CD4+ T cell subset(s) developing during the course of CIA, lymph nodes from susceptible DBA/1 mice (H-2q) were harvested at different times after injection of bovine type II collagen in Freund's complete adjuvant and checked by enzyme-linked immunospot assay for the production of interferon (IFN)-gamma and interleukin (IL)-4. The results clearly showed that type II collagen-specific T cells secreting either IFN-gamma, IL-4, or both, develop early in vivo, before the onset of arthritis: the number of IFN-gamma-secreting cells was already maximal 15 days after immunization, whereas more IL-4-secreting cells were found at day 30, just before the onset of clinical arthritis. Another strategy was to establish collagen-specific CD4+ T cell lines and sublines in vitro and to analyze their lymphokine secretion pattern. Lines generated 8 days after immunization displayed a mixed lymphokine secretion pattern characteristic of Th0 cells or of a mixture of Th1 and Th2 cells. After limiting dilution of a day 8 line, 60% of the growing sublines were Th0-like (secreting IFN-gamma, IL-4, and IL-5), and 25% were Th1 (secreting IFN-gamma). By day 25 post-immunization, 33% of the generated sublines were Th0-like, 11% Th1, and 56% Th2 (secreting IL-4 and IL-5). Moreover, all the sublines raised from the lymph nodes of arthritic mice harvested at day 55 secreted high amounts of Th2 lymphokines, and only 3 out of 14 also produced some IFN-gamma. This study demonstrates that during the course of CIA the collagen-specific CD4+ T cell response shifts in vivo from a dominant Th0/Th1 response to a clear Th2 phenotype. These results contribute to our understanding of the collagen-specific CD4+ T helper subsets which develop during the induction and clinical phases of CIA.
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PMID:Conversion in vivo from an early dominant Th0/Th1 response to a Th2 phenotype during the development of collagen-induced arthritis. 920 98

We have shown that TAK-603, a new anti-rheumatic drug, is more effective in animal models in which cellular immunity plays a central role. Here, we studied the effect of the drug on Th1 cytokines, which are dominantly produced in this type of immune reaction, in an in vitro system and an in vivo model. We established Th1- and Th2-dominant T-cell lines, and studied the effect of TAK-603 on their cytokine production. Th1 cell lines were BALB/c mouse allo-reactive T cells and C57BL mouse mite antigen-reactive T cells, and the Th2 cell line was BALB/c mouse ovalbumin-reactive T cells. TAK-603 suppressed the production of Th1 cytokines [interferon-gamma (IFN-gamma) and interleukin-2 (IL-2)] and not that of Th2 cytokines (IL-4, IL-5) in these cell lines. Furthermore, selective suppression of Th1 cytokine production was also observed in the T-cell clones obtained from the ovalbumin-reactive T-cell line. To investigate the effect on cytokine production in animal models of arthritis, we analysed the expression of cytokine messenger RNA using reverse transcription-polymerase chain reaction. In adjuvant arthritis rats, Th1-dominant cytokine production was observed both in the arthritic joint and the spleen, and the time-course paralleled the progression of arthritis. On the other hand, in type-II collagen-induced arthritis, in which TAK-603 has little effect, Th1-dominant cytokine production was not observed and Th2 cytokines were shown to be more important. The adjuvant arthritis rats treated with TAK-603 (6.25 mg/kg/day, per os) showed significantly lower cytokine mRNA expression both locally and systemically. These data suggest that TAK-603 selectively suppresses Th1 cytokine production, which is consistent with its effect on cellular immunity in animal models.
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PMID:TAK-603 selectively suppresses Th1-type cytokine production and inhibits the progression of adjuvant arthritis. 937 Sep 27

Previous studies showed that mice with pristane-induced arthritis (PIA) and those protected from the disease by preimmunization with mycobacterial 65-kDa heat shock protein (hsp65), possess raised immune responses to hsp65. Thus, a paradox exists whereby T cells from both arthritic and hsp65-protected animals proliferate vigorously in response to the same Ag. Here we demonstrate that T cells from mice with PIA and hsp65-protected mice produce different cytokines in vitro in response to hsp65. The use of a sensitive CelELISA to measure Ag-driven lymphokine production revealed that spleen cells from hsp65-protected mice, but not those from pristane-injected or normal mice, produced the Th2-associated cytokines IL-4, IL-5, and IL-10 in response to stimulation with hsp65. By contrast, the Th1-associated cytokines IL-2 and IFN-gamma were produced by spleen cells from mice of all groups in response to hsp65. Furthermore, there was a dramatic increase in the IgG1 to IgG2a ratio of anti-hsp65 Abs from arthritic to protected mice. Thus, it appears that a Th2 response is protective against PIA. To examine this theory, a regimen of IL-12 administration which polarizes the hsp65-specific (Th2) immune response toward Th1 was identified. This regime abolished hsp65-mediated protection against PIA. Other experiments revealed that the specificity of the response to hsp65 was important, as other bacterial proteins known not to protect against PIA induced similar Th2-associated cytokines in vitro. It is considered that the protection afforded by hsp65 preimmunization is mediated by Th2-associated cytokines produced by hsp65-specific CD4+ T cells.
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PMID:CD4+ Th2 cells specific for mycobacterial 65-kilodalton heat shock protein protect against pristane-induced arthritis. 937 54

T helper cell type 1 (Th1) and 2 (Th2) are central to immune regulation. However, no stable cell surface marker capable of distinguishing and separating these two subsets of CD4(+) cells has yet been found. Using differential display PCR, we have identified a gene encoding a cell membrane bound molecule, originally designated ST2L, T1, DER4, or Fit, expressed constitutively and stably on the surface of murine Th2s, but not Th1s even after stimulation with a range of immunological stimuli. Antibody against a peptide derived from ST2L strongly and stably labeled the surface of cloned Th2s but not Th1s, and Th2s but not Th1s derived from naive T cells of ovalbumin T cell receptor-alpha/beta transgenic mice. Three-color single cell flow cytometric analysis shows that cell surface ST2L coexpressed with intracellular interleukin (IL)-4, but not with interferon (IFN)-gamma. The antibody selectively lysed Th2s in vitro in a complement-dependent manner. In vivo, it enhanced Th1 responses by increasing IFN-gamma production and decreasing IL-4 and IL-5 synthesis. It induced resistance to Leishmania major infection in BALB/c mice and exacerbated collagen-induced arthritis in DBA/1 mice. Thus, ST2L is a stable marker distinguishing Th2s from Th1s and is also associated with Th2 functions. Hence, it may be a target for therapeutic intervention.
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PMID:Selective expression of a stable cell surface molecule on type 2 but not type 1 helper T cells. 948 Sep 88

Previous studies showed that mice with pristane-induced arthritis (PIA) and those protected from the disease by preimmunization with mycobacterial 65-kDa heat shock protein (hsp65) possess raised immune responses to hsp65. Additionally, T cells from hsp65-protected mice, but not from pristane-injected or normal mice, produced the Th2-associated cytokines IL-4, IL-5, and IL-10 in response to stimulation with hsp65. Here we demonstrate that the specificity of the immune response to hsp65 and related heat shock protein (hsps) differs between protected and PIA mice. T cells from hsp65-protected mice respond to the bacterial hsps tested but not to the mammalian homologue, hsp58. Similarly, they exhibit high serum titers of anti-hsp65 Abs, yet they have virtually undetectable levels of anti-hsp58 IgG. By contrast, both cellular and humoral immune responses are detectable to bacterial and mammalian hsps in mice with PIA. An immunodominant T cell epitope has been identified in hsp65-protected mice corresponding to amino acids 261-271 from hsp65. Immunization of mice, either before or after the induction of arthritis, with this bacterial peptide, but not its mammalian homologue, protects mice from the development of PIA, and protection is associated with the production of Th2-type cytokines. Other experiments revealed that T cells primed with bacterial 261-271 or the mammalian homologue do not cross-react at the proliferative or cytokine level. These results demonstrate that an hsp65 peptide-specific Th2 response confers protection from PIA but do not support the idea that protection is mediated by a cross-reaction with self hsp58 in the joints.
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PMID:An immunodominant epitope from mycobacterial 65-kDa heat shock protein protects against pristane-induced arthritis. 957 71

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