Prevention and amelioration of collagen‐induced arthritis by blockade of the CD28 co‐stimulatory pathway: requirement for both B7‐1 and B7‐2

Webb, Louise M. C.; Walmsley, Marita J.; Feldmann, Marc

doi:10.1002/eji.1830261008

Cited by 222 publications

(193 citation statements)

References 56 publications

(18 reference statements)

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“…In many animal models of arthritis, CD28 acts as a classic essential costimulatory protein in permitting the TCR-dependent responses to collagen that are required for initiation and progression of joint inflammation (36)(37)(38)(39). Trials with CTLA-4Ig blockade of CD28 signaling in RA have been extremely promising, but the mechanism of its therapeutic activity in humans has yet to be assessed (13,14).…”

Section: Discussionmentioning

confidence: 99%

CTLA‐4IG suppresses reactive oxygen species by preventing synovial adherent cell–induced inactivation of rap1, a ras family GTPASE mediator of oxidative stress in rheumatoid arthritis T cells

Remans¹,

Wijbrandts²,

Sanders³

et al. 2006

Arthritis & Rheumatism

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Objective. Oxidative stress contributes to the inflammatory properties of rheumatoid arthritis (RA) synovial T lymphocytes. This study was undertaken to investigate the mechanisms leading to production of reactive oxygen species (ROS) and oxidative stress in RA synovial T lymphocytes.Methods. ROS production in T lymphocytes from the peripheral blood (PB) of healthy donors and from the PB and synovial fluid (SF) of RA patients was measured by ROS-dependent fluorescence of 6-carboxy-2 ,7 -dichlorofluorescein. Rap1 GTPase activation was assessed by activation-specific probe precipitation. Proliferation of RA PB and SF T lymphocytes was assayed by 3 H-thymidine incorporation. In some experiments, RA PB T cells were preincubated with autologous SF or with PB or SF adherent cells. Experiments were performed in the absence or presence of transwell membranes or CTLA-4Ig fusion proteins. Short-and longterm stimulations of healthy donor PB T lymphocytes were performed with inflammatory cytokines, in the absence or presence of activating anti-CD28 antibodies. Conclusion. Cell-cell contact between T cells and RA synovial adherent cells mediates Rap1 inactivation and subsequent ROS production in T lymphocytes following exposure to inflammatory cytokines. This process can be blocked by CTLA4-Ig fusion protein. Results. T lymphocyte ROS production and

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Section: Discussionmentioning

confidence: 99%

CTLA‐4IG suppresses reactive oxygen species by preventing synovial adherent cell–induced inactivation of rap1, a ras family GTPASE mediator of oxidative stress in rheumatoid arthritis T cells

Remans¹,

Wijbrandts²,

Sanders³

et al. 2006

Arthritis & Rheumatism

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“…CD28-deficient DBA/1 mice do not develop CIA, suggesting an absolute requirement for costimulation provided by CD28 for autoantigen-specific CD4 ϩ T cell activation and development of disease in this model (21). The prevention and amelioration of collageninduced arthritis by blockade of the CD28 costimulatory pathway have been observed (22), but not confirmed by others (23).…”

mentioning

confidence: 85%

Requirement for CD28 May Not Be Absolute for Collagen-Induced Arthritis: Study with HLA-DQ8 Transgenic Mice

Taneja¹,

Taneja

Behrens³

et al. 2005

The Journal of Immunology

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CD28 is required to achieve optimal T cell activation to an Ag. To determine the role CD28 costimulation plays in collagen-induced arthritis, we have generated DQ8 transgenic, CD28-deficient mice. DQ8 mice deficient for CD28 had comparable numbers of CD4 and CD8 T cells as DQ8.CD28+/+ mice. DQ8.CD28−/− mice develop collagen-induced arthritis with delayed onset and less severity than DQ8.CD28+/+ mice. T cells from DQ8.CD28−/− mice did not respond to type II collagen efficiently in vitro, although the response to DQ8-restricted peptides was similar to that in the parent mice. There was no functional defect in T cells as observed by proliferation with Con A. Cytokine analysis from in vitro study showed the production of high levels of the inflammatory cytokine, IFN-γ, in response to type II collagen. We observed an increase in CD4+CD28−NKG2D+ cells after immunization, suggesting an important role for cells bearing this receptor in the disease process. CD28−/− mice also have an increased number of DX5+ cells compared with CD28+/+ mice, which can lead to the production of high levels of IFN-γ. DQ8.CD28−/− mice had an increased number of cells bearing other costimulatory markers. Cells from DQ8.CD28−/− mice exhibited a lower proliferation rate and were resistant to activation-induced cell death compared with DQ8.CD28+/+ mice. This study supports the idea that CD28 plays a crucial role in the regulation of arthritis. However, in the absence of CD28 signaling, other costimulatory molecules can lead to the development of disease, thus indicating that the requirement for CD28 may not be absolute in the development of arthritis.

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“…Studies in animal models proved its efficacy in dampening the manifestations of arthritis. Administration of CTLA-4Ig in mice at the time of the first collagen injection prevented the development of CIA (113). When treatment was delayed until arthritis had developed, CTLA-4Ig was still able to ameliorate disease.…”

Section: From Animal Models Toward the Clinicmentioning

confidence: 99%

Evaluation of therapeutic targets in animal models of arthritis: How does it relate to rheumatoid arthritis?

Bevaart¹,

Vervoordeldonk²,

Tak³

2010

Arthritis & Rheumatism

222

193

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There are accumulating data describing the association between diabetes and cancer mortality from Westernised populations. There are no data describing the relationship between diabetes and cancer mortality in African or South Asian populations from developing countries. We explored the relationship of abnormal glucose tolerance and diabetes on cancer mortality risk in a large, multi‐ethnic cohort from the developing nation of Mauritius. Population‐based surveys were undertaken in 1987, 1992 and 1998. The 9559 participants comprised 66% of South Asian (Indian), 27% of African (Creole), and 7% of Chinese descent. Cox's proportional hazards model with time varying covariates was used to obtain hazard ratios (HRs) and 95% confidence intervals (95% CI) for risk of cancer mortality, after adjustment for confounding factors. In men, but not women, cancer mortality risk increased with rising 2h‐PG levels with HR for the top versus bottom quintile of 2.77 (95%CI: 1.28 to 5.98). South Asian men with known diabetes had a significantly greater risk of cancer mortality than those with normal glucose tolerance (NGT) HR: 2.74 (95%CI: 1.00‐7.56). Overall, impaired glucose tolerance was associated with an elevated risk of cancer mortality compared to NGT (HR: 1.47, 95% CI: 0.98–2.19), though this was not significant. We have shown that the association between abnormal glucose tolerance and cancer extends to those of African and South Asian descent. These results highlight the importance of understanding this relationship in a global context to direct future health policy given the rapid increase in type 2 diabetes, especially in developing nations.

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Prevention and amelioration of collagen‐induced arthritis by blockade of the CD28 co‐stimulatory pathway: requirement for both B7‐1 and B7‐2

Cited by 222 publications

References 56 publications

CTLA‐4IG suppresses reactive oxygen species by preventing synovial adherent cell–induced inactivation of rap1, a ras family GTPASE mediator of oxidative stress in rheumatoid arthritis T cells

CTLA‐4IG suppresses reactive oxygen species by preventing synovial adherent cell–induced inactivation of rap1, a ras family GTPASE mediator of oxidative stress in rheumatoid arthritis T cells

Requirement for CD28 May Not Be Absolute for Collagen-Induced Arthritis: Study with HLA-DQ8 Transgenic Mice

Evaluation of therapeutic targets in animal models of arthritis: How does it relate to rheumatoid arthritis?

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