Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement

The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.


CTLA4-Ig Modifies Dendritic Cells From Mice with Collagen-Induced Arthritis to Increase the CD4CD25Foxp3 Regulatory T Cell Population

Park1,  Kyung-Su, Cho2,  Mi-La, Lee1,  Chang-Hoon, Kim1,  Ji-Min, Yoon1,  Ho-Sung, Kang1,  Kwi-Young, Kwok1,  Seung-Ki

Seoul St. Mary's Hospital, The Catholic University of Korea, Seoul, South Korea
Catholic Institute of Medical Sciences, The Catholic University of Korea, Seoul, South Korea
Daejeon St. Mary's Hospital, Daejeon, South Korea
Uijeongbu St. Mary's Hospital, Uijeongnbu, South Korea
Holy Family Hospital, Bucheon, South Korea
Incheon St. Mary's Hospital, Incheon, South Korea
Konkuk University Hospital, Seoul, South Korea
Kangnam St Mary's Hosp, Seoul, South Korea

Purpose:

CTLA4-Ig is a therapeutic agent used in the treatment of rheumatoid arthritis. It binds to B7 molecule and induces dendritic cells (DCs) to express indoleamine 2,3-dioxygenase (IDO), which is known to be involved in the generation of CD4+CD25+Foxp3+ regulatory T cells (Tregs). In this study, we investigated whether CTLA4-Ig increased CD4+CD25+Foxp3+ Treg population in collagen-induced arthritis (CIA) mouse model.

Method:

CTLA4-Ig or PBS was administered into CIA-induced mice and then arthritis index was measured and CD4+CD25+Foxp3+ Treg and CD4+IL-17+T cell population were examined in the joint and the spleen. DCs and CD4+T cells from CIA mice were cultured with anti-CD3 in the presence of CTLA4-Ig or control-Ig and then CD4+CD25+Foxp3+ Treg population were examined. Spleen DCs from CIA mice were pretreated with CTLA4-Ig and then adoptively transferred into CIA-induced mice. Arthritis index was measured and CD4+CD25+Foxp3+ Treg and CD4+IL-17+T cell population were examined in the spleen of DC-transferred mice.

Results:

CTLA4-Ig suppressed CIA and increased the CD4+CD25+Foxp3+ Treg population, but decreased the CD4+IL-17+ T cell population. When DCs and CD4+T cells from CIA mice were cultured with anti-CD3, CTLA4-Ig increased the CD4+CD25+Foxp3+ Treg population in a TGF-beta-dependent, IDO-independent manner, but control-Ig did not. When adoptively transferred, CTLA4-Ig-treated DCs suppressed CIA and increased the CD4+CD25+Foxp3+ Treg population but untreated DCs did not.

Conclusion:

CTLA4-Ig suppressed CIA by modifying DCs from CIA mice to increase CD4+CD25+Foxp3+Treg population.

To cite this abstract, please use the following information:
Park, Kyung-Su, Cho, Mi-La, Lee, Chang-Hoon, Kim, Ji-Min, Yoon, Ho-Sung, Kang, Kwi-Young, et al; CTLA4-Ig Modifies Dendritic Cells From Mice with Collagen-Induced Arthritis to Increase the CD4CD25Foxp3 Regulatory T Cell Population [abstract]. Arthritis Rheum 2009;60 Suppl 10 :13
DOI: 10.1002/art.25096

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