Adoptive Transfer of Susceptibility to Antigen-Induced Arthritis into Severe Combined Immunodeficient (SCID) MICE: Role of CD4+ and CD8+ T Cells

Petrow, Peter; Thoss, K.; Katenkamp, D.; Bräuer, Rolf

doi:10.3109/08820139609059316

Cited by 38 publications

(44 citation statements)

References 4 publications

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“…Because AIA is characterized as a Th1-dependent experimental model of joint disease (43,44), the demonstration of a suppressive IL-10 orientated T cell response in ASC Ϫ/Ϫ mice could be a possible link to the observed reduced inflammatory status in these animals, although we cannot directly correlate this altered T cell phenotype in ASC Ϫ/Ϫ mice with their milder disease outcome. Our results are in agreement with previous studies that have shown that the development of Th1-mediated experimental arthritis is critically linked with the balance of cytokines produced by Th1/ Th2 cells (45)(46)(47).…”

Section: Discussionmentioning

confidence: 72%

Inflammatory Role of ASC in Antigen-Induced Arthritis Is Independent of Caspase-1, NALP-3, and IPAF

Kolly¹,

Karababa²,

Joosten

et al. 2009

The Journal of Immunology

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Because IL-1β plays an important role in inflammation in human and murine arthritis, we investigated the contribution of the inflammasome components ASC, NALP-3, IPAF, and caspase-1 to inflammatory arthritis. We first studied the phenotype of ASC-deficient and wild-type mice during Ag-induced arthritis (AIA). ASC−/− mice showed reduced severity of AIA, decreased levels of synovial IL-1β, and diminished serum amyloid A levels. In contrast, mice deficient in NALP-3, IPAF, or caspase-1 did not show any alteration of joint inflammation, thus indicating that ASC associated effects on AIA are independent of the classical NALP-3 or IPAF inflammasomes. Because ASC is a ubiquitous cytoplasmic protein that has been implicated in multiple cellular processes, we explored other pathways through which ASC may modulate inflammation. Ag-specific proliferation of lymph node and spleen cells from ASC-deficient mice was significantly decreased in vitro, as was the production of IFN-γ, whereas IL-10 production was enhanced. TCR ligation by anti-CD3 Abs in the presence or absence of anti-CD28 Abs induced a reduction in T cell proliferation in ASC−/− T cells compared with wild-type ones. In vivo lymph node cell proliferation was also significantly decreased in ASC−/− mice, but no effects on apoptosis were observed either in vitro or in vivo in these mice. In conclusion, these results strongly suggest that ASC modulates joint inflammation in AIA through its effects on cell-mediated immune responses but not via its implication in inflammasome formation.

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Section: Discussionmentioning

confidence: 72%

Inflammatory Role of ASC in Antigen-Induced Arthritis Is Independent of Caspase-1, NALP-3, and IPAF

Kolly¹,

Karababa²,

Joosten

et al. 2009

The Journal of Immunology

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“…However, the overwhelming influx of neutrophils, as opposed to T cells, into the joints throughout a 5-day period of AIA is surprising, given the observations that arthritis cannot be induced in nonimmunized mice by i.a. mBSA injection (39) and that susceptibility can be adoptively trasferred by CD4 ϩ T cells from AIA donors to SCID mice (62). One of the possible explanations for the predominance of joint-homing neutrophils in this otherwise T cell-dependent model of arthritis is the presence of immune compexes (ICs).…”

Section: Discussionmentioning

confidence: 99%

Expression of L-Selectin, but Not CD44, Is Required for Early Neutrophil Extravasation in Antigen-Induced Arthritis

Szántó

Gál

Gonda

et al. 2004

The Journal of Immunology

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L (leukocyte)-selectin (CD62L) and CD44 are major adhesion receptors that support the rolling of leukocytes on endothelium, the first step of leukocyte entry into inflamed tissue. The specific contribution of L-selectin or CD44 to the regulation of cell traffic to joints in arthritis has not been investigated. We used CD44-deficient, L-selectin-deficient, and CD44/L-selectin double knockout mice to determine the requirement for these receptors for inflammatory cell recruitment during Ag-induced arthritis. Intraperitoneal immunization resulted in similar activation status and Ag-specific responses in wild-type and gene-targeted mice. However, extravasation of neutrophil granulocytes, but not the emigration of T cells, into the knee joints after intra-articular Ag injection was significantly delayed in L-selectin-deficient and double knockout mice. Intravital videomicroscopy on the synovial microcirculation revealed enhanced leukocyte rolling and diminished adherence in mice lacking either CD44 or L-selectin, but CD44 deficiency had no significant effect on the recruitment of L-selectin-null cells. Compared with wild-type leukocytes, expression of L-selectin was down-regulated in CD44-deficient cells in the spleen, peripheral blood, and inflamed joints, suggesting that reduced expression of L-selectin, rather than the lack of CD44, could be responsible for the delayed influx of granulocytes into the joints of CD44-deficient mice. In conclusion, there is a greater requirement for L-selectin than for CD44 for neutrophil extravasation during the early phase of Ag-induced arthritis.

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“…The AIA model is dependent on CD4ϩ T cells and Th1-type immunity, as well as the presence of mBSA-specific antibodies and mBSA immune complexes in the serum and joint tissues of animals with established disease (19,46). A role for presentation of autoantigen has been hypothesized in AIA based on increased T cell responses to type II collagen and proteoglycan in arthritic animals (47).…”

Section: Discussionmentioning

confidence: 99%

Antigen‐specific suppression of established arthritis in mice by dendritic cells deficient in NF‐κB

Martin

Capini

Duggan

et al. 2007

Arthritis & Rheumatism

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Objective. NF-B inhibitors applied to animal models of rheumatoid arthritis (RA) demonstrate the important role of NF-B in the production of mediators of inflammation in the joint and their antiinflammatory effects. Because NF-B is involved in the differentiation, activation, and survival of almost all cells, its prolonged inhibition might have unwanted adverse effects. Therefore, we sought to apply NF-B inhibitors more specifically, targeting dendritic cell (DC) differentiation, in order to influence the outcome of the autoimmune response, rather than to produce a broad antiinflammatory effect. We tested whether DCs treated with the NF-B inhibitor BAY 11-7082 and exposed to arthritogenic antigen would suppress established arthritis in C57BL/6 mice.Methods. Antigen-induced arthritis was generated in C57BL/6 mice by injection of methylated bovine serum albumin (mBSA). After mBSA challenge, mouse knee joints were injected with antigen-exposed BAY 11-7082-treated DCs or with soluble tumor necrosis factor receptor (sTNFR). Intraarticular injection of interleukin-1 (IL-1) was used to induce disease flare.Results. Inflammation and erosion were suppressed in mice that received mBSA-exposed BAY 11-7082-treated DCs, but not in those that received keyhole limpet hemocyanin-exposed BAY 11-7082-treated DCs. Clinical improvement was dependent on IL-10 and was associated with antigen-specific suppression of the delayed-type hypersensitivity (DTH) reaction and switching of anti-mBSA antibody isotype from IgG2b to IgG1 and IgA. Suppression of the DTH reaction or arthritic disease was not impaired by concomitant administration of sTNFR. Suppression could be reversed with intraarticular administration of IL-1␤ and could be restored by a second injection of mBSA-exposed BAY 11-7082-treated DCs.Conclusion. BAY 11-7082-treated DCs induce antigen-specific immune suppression in this model of inflammatory arthritis, even after full clinical expression of the disease. Such DCs have potential as antigenspecific therapy for autoimmune inflammatory arthritis, including RA.

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Adoptive Transfer of Susceptibility to Antigen-Induced Arthritis into Severe Combined Immunodeficient (SCID) MICE: Role of CD4+ and CD8+ T Cells

Cited by 38 publications

References 4 publications

Inflammatory Role of ASC in Antigen-Induced Arthritis Is Independent of Caspase-1, NALP-3, and IPAF

Inflammatory Role of ASC in Antigen-Induced Arthritis Is Independent of Caspase-1, NALP-3, and IPAF

Expression of L-Selectin, but Not CD44, Is Required for Early Neutrophil Extravasation in Antigen-Induced Arthritis

Antigen‐specific suppression of established arthritis in mice by dendritic cells deficient in NF‐κB

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