Role of T lymphocytes in murine collagen induced arthritis

Holmdahl, Rikard; Klareskog, Lars; Rubin, Kristofer; Björk, Jakob; Smedegård, G.; Jönsson, Roland; Andersson, Mikael

doi:10.1007/bf01971231

Cited by 57 publications

(28 citation statements)

References 46 publications

(49 reference statements)

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“…Although autoantibodies are important for initiating joint inflammation by binding to cartilage and initiating inflammation through Fc␥R-dependent pathways (55), there is little agreement as to whether individual collagen-specific autoantibody isotypes or their titers cause or correlate with disease severity in CIA (24). In fact, collagen-specific IgG1, IgG2a, and IgG2b Abs alone can induce transient arthritis in recipient mice (19,26,27), with collagen-reactive T cells required for normal CIA induction and progression (19). Although CIA and anti-collagen Ab-induced arthritis in the absence of B cell function exacerbates disease (19,56), B cell depletion before or following collagen immunization did not exacerbate arthritis development, joint inflammation, distortion, or ankylosis (Figs.…”

Section: Discussionmentioning

confidence: 99%

“…In addition, IFN-␥-deficient B6 mice treated with CD22 mAbs conjugated with calicheamicin toxin do not develop CIA (24), implying that B cells play a pivotal role in the disease. Transferring collagen-specific autoantibodies alone leads to transient arthritis, with a histopathology that is somewhat different from that of CIA (19,(25)(26)(27)(28). Thus, synergies between humoral and cell-mediated immunity appear critical for CIA, although the role(s) for B cells in CIA induction or pathogenesis remain poorly understood (26,29).…”

Section: R Heumatoid Arthritis (Ra)mentioning

confidence: 99%

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B Cell Depletion Delays Collagen-Induced Arthritis in Mice: Arthritis Induction Requires Synergy between Humoral and Cell-Mediated Immunity

Yanaba¹,

Hamaguchi²,

Venturi³

et al. 2007

The Journal of Immunology

130

129

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Rheumatoid arthritis is a systemic autoimmune disease. B cells are likely to play a critical role in arthritis pathogenesis, although it is unclear whether they are necessary for disease induction, autoantibody production, or disease progression. To assess the role of B cells in inflammatory arthritis, B cells were depleted using mouse anti-mouse CD20 mAbs in a mouse model of collagen-induced arthritis. CD20 mAbs effectively depleted mature B cells from adult DBA-1 mice. When B cells were depleted using CD20 mAbs before collagen immunization, there was a delay in disease onset and autoantibody production, with significantly diminished severity of arthritis both clinically and histologically. B cell depletion further delayed disease onset if initiated before, as well as after, collagen immunization. However, in both cases, the eventual reappearance of peripheral B cells triggered autoantibody production and the subsequent development of arthritis in collagen-sensitized mice. By contrast, B cell depletion after collagen immunizations did not have a significant effect on arthritis progression or severity. Thus, disease symptoms were only induced when peripheral B cells and their autoantibody products were present in collagen-immunized mice, documenting a critical role for B cells during the elicitation phase of collagen-induced arthritis. These studies suggest that B cell depletion strategies will be most effective when initiated early in the development of inflammatory arthritis, with sustained B cell depletion required to inhibit the production of isotype-switched pathogenic Abs and the evolution of joint inflammation and destruction.

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Section: Discussionmentioning

confidence: 99%

Section: R Heumatoid Arthritis (Ra)mentioning

confidence: 99%

B Cell Depletion Delays Collagen-Induced Arthritis in Mice: Arthritis Induction Requires Synergy between Humoral and Cell-Mediated Immunity

Yanaba¹,

Hamaguchi²,

Venturi³

et al. 2007

The Journal of Immunology

130

129

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“…The arthritic lesions in this model bear resemblance to some of the lesions of rheumatoid arthritis in man. Both the cellular and T-cell-dependent immune responses to type II collagen are critical for the pathogenesis of the disease (4).…”

mentioning

confidence: 99%

Restricted heterogeneity in T-cell antigen receptor V beta gene usage in the lymph nodes and arthritic joints of mice.

Haqqi

Anderson

Banerjee

et al. 1992

Proc. Natl. Acad. Sci. U.S.A.

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We have used PCR to study the expression of T-cell antigen receptor 13 RNA containing particular variable region (V) elements from transcripts directly in the cells isolated from joints and lymph nodes of B1O.Q mice (H-2r) immunized with chicken type II collagen. Our data show that the T cells present in arthritic joints expressed only a few '$ transcripts -'2, -6, -7, -8.2, -9, -10, and -15. 6 and -8.2 were expressed predominantly (six out ofseven animals) while others were expressed at a relatively low level in different animals. In lymph node cells, transcripts for $j6, -8.2, and -9 were detected in four out of seven animals. The data indicate that in collageninduced arthritis there is a restrictive usage of TCR $ elements and that *6 and -8.2 are probably used preferentially.Collagen-induced arthritis (CIA) was first described by Trentham et al. (1) in 1977 and has subsequently been induced in mice and primates (2, 3). CIA ensues after immunization of susceptible strains of mice and rats with type II collagen in Freund's adjuvant (1, 2). The arthritic lesions in this model bear resemblance to some of the lesions of rheumatoid arthritis in man. Both the cellular and T-cell-dependent immune responses to type II collagen are critical for the pathogenesis of the disease (4).Susceptibility to the development of an autoimmune disorder has been found to have a distinct genetic basis, both in humans and in animal models of the disease. In mouse, induction of CIA is linked to the major histocompatibility complex (MHC) and has been mapped to the I-A subregion by using various recombinant strains, and it has been shown that only H-2 and H-2r haplotypes develop CIA after immunization with type II collagen (4, 5). In other haplotypes, immunization with heterologous type II collagen induces an autoantibody response but never progresses to the development of arthritis (6, 7). These results indicate that the induction of CIA is dependent on the activation of I-A-restricted self-type-II-collagen-reactive T cells. Furthermore, in another study, Seki et al. (8) have proposed that there is a synergistic effect between humoral and cell-mediated immunity on the induction and perpetuation of CIA.We have earlier reported that the T-cell antigen receptor (TCR) variable region 18 chain (Vs) genes apparently play a vital role in the susceptibility to the induction of CIA (9). We have also shown that inbred strains of mice with the susceptible MHC haplotype but with the genomic deletion of TCR Vp genes were resistant to the induction of arthritis, indicating that TCR Vp genes play an important, perhaps crucial, role in the pathogenesis of arthritis (10-12). In this communication, we report that the T cells present in arthriticjoint and draining lymph nodes (LNs) of mice express a restricted repertoire of TCR Vp genes.MATERIALS AND METHODS Mice. B10.Q mice (H-2q) were bred and maintained in the mouse colony at Mayo Clinic (Rochester, MN). Male mice (6 to 8 weeks old) were used in the present study. Age-and sex-matched mic...

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“…The production of large amounts of anti-CIl antibody alone does not always predict or associate with disease in collagen induced arthritis [5,23,24] but there is direct evidence from antibody or immune complex transfer experiments thai anti-CIl antibodies do contribute to pathology [7,25,26]. The amount of antibody must be critical in this, but the present experiments suggest that low-affinity antibodies are especially itnportant pathologically.…”

Section: Discussionmentioning

confidence: 63%

“…respectively [2], Several lines of evidence show thai T cells are involved in the initiation or maintenance of joint destruction or both; athymic rats are refractory lo disease induction by active immunization with CII [3]: passive treatment with anti-thymocyte antiserum decreases the incidence of disease, serum antibody litres and delayed-type hypersensitiviiy to CII in rats [4] and cells of CIlspecific T cell clones or lines can induce disease in normal or irradiated rals and mice [5].…”

Section: Introductionmentioning

confidence: 99%

Low-affinity antibodies against collagen type II produced by lymph node cells are associated with pathology in collagen-induced arthritis in rats

Rahman

Loh

Staines

1992

Clinical and Experimental Immunology

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SUMMARYThe relalionship between the aiifinily of antibodies againsl type II collagen (CM) and arthritis was studied in rats immunized intradermally with bovine CM. Disease was associated with a higher tneaii titre of serum antibody and a lower mean functional antibody affinity (determined in a chaotropic dissociation assay) againsl both the immunizing bovine CI I and homologousautoantigenicrat ClI in comparison with the response in immunized rats that did noi develop disease. The functional affinity of the antibodies present in the serum was found to correlate with that of antibodies produced in culture by ceils from the lymph nodesdraining the site of immunization wilh collagen. The reduction in mean functional affinity in Ihe anti-collagen responsemay be the result ofthe increased production of aniibodies of the lowest affinity and a consequent broadening of the affinity heterogeneity. It is proposed that production of low-affinity antibodies in the lymph nodes draining the site of immunization wilh colhigcn is important in the pathogenesis of collagen-induced arthritis in rats.

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Role of T lymphocytes in murine collagen induced arthritis

Cited by 57 publications

References 46 publications

B Cell Depletion Delays Collagen-Induced Arthritis in Mice: Arthritis Induction Requires Synergy between Humoral and Cell-Mediated Immunity

B Cell Depletion Delays Collagen-Induced Arthritis in Mice: Arthritis Induction Requires Synergy between Humoral and Cell-Mediated Immunity

Restricted heterogeneity in T-cell antigen receptor V beta gene usage in the lymph nodes and arthritic joints of mice.

Low-affinity antibodies against collagen type II produced by lymph node cells are associated with pathology in collagen-induced arthritis in rats

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