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Abstract

Effective treatment of adjuvant arthritis with a stimulatory CD28-specific monoclonal antibody.

Marta Rodríguez-Palmero, Angels Franch, Margarida Castell, Carme Pelegrí, Francisco J Pérez-Cano, Christoph Kleinschnitz, Guido Stoll, Thomas Hünig and Cristina Castellote
The Journal of Rheumatology January 2006, 33 (1) 110-118;
Marta Rodríguez-Palmero
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Angels Franch
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Margarida Castell
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Carme Pelegrí
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Francisco J Pérez-Cano
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Christoph Kleinschnitz
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Guido Stoll
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Thomas Hünig
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Cristina Castellote
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Abstract

OBJECTIVE: To determine the immunomodulatory effects of the anti-rat CD28 monoclonal antibody (Mab) JJ316 on the onset of rat adjuvant arthritis (AA). JJ316 is a superagonistic Mab that induces polyclonal T cell proliferation in the absence of T cell receptor (TCR) ligation and promotes the expansion of regulatory T cells. METHODS: Female Wistar rats in which AA was induced were treated with JJ316 on Day 0 and Day 9 postinduction. A parallel treatment with JJ319, a "conventional" CD28-specific Mab that costimulates anti-TCR triggered proliferation, was performed. Severity of arthritis was monitored by means of an arthritic score, and by recording hindpaw volume and body weight increases. Serum antibodies against the AA-inducing mycobacteria were also determined by ELISA. To ascertain the effect of JJ316 on T lymphocytes in vivo, blood CD4+CD45RChigh (Th1-like) and CD4+CD45RClow (Th2-like) cells were analyzed by flow cytometry, and the relative levels of interleukin 2 (IL-2), IL-10, and interferon-g (IFN-g) mRNA in synovial tissue were measured by real-time reverse transcription-polymerase chain reaction. RESULTS: JJ316 efficiently prevented the inflammatory process of AA. This effect was associated with a specific decrease in the blood CD4+CD45RChigh/CD4+CD45RClow T cell ratio and high IL-10 mRNA expression in the synovia. In addition, anti-mycobacteria antibody levels decreased in JJ316 treated animals. In contrast, administration of the conventional anti-CD28 Mab JJ319 did not improve inflammation. CONCLUSION: JJ316, a stimulatory CD28-specific Mab known to promote Th2 function and the expansion of regulatory T cells, provides effective protection from AA.

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The Journal of Rheumatology
Vol. 33, Issue 1
1 Jan 2006
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Effective treatment of adjuvant arthritis with a stimulatory CD28-specific monoclonal antibody.
Marta Rodríguez-Palmero, Angels Franch, Margarida Castell, Carme Pelegrí, Francisco J Pérez-Cano, Christoph Kleinschnitz, Guido Stoll, Thomas Hünig, Cristina Castellote
The Journal of Rheumatology Jan 2006, 33 (1) 110-118;

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Effective treatment of adjuvant arthritis with a stimulatory CD28-specific monoclonal antibody.
Marta Rodríguez-Palmero, Angels Franch, Margarida Castell, Carme Pelegrí, Francisco J Pérez-Cano, Christoph Kleinschnitz, Guido Stoll, Thomas Hünig, Cristina Castellote
The Journal of Rheumatology Jan 2006, 33 (1) 110-118;
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