ババ ノブヤス
  馬場 伸育
   所属   川崎医科大学  医学部 基礎医学 免疫学
   職種   講師
論文種別 原著
言語種別 英語
査読の有無 査読あり
表題 CD28 co-stimulation down regulates Th17 development.
掲載誌名 正式名:PloS one
略  称:PLoS One
ISSNコード:19326203/19326203
掲載区分国外
巻・号・頁 4(3),pp.e5087
著者・共著者 Salim Bouguermouh, Geneviève Fortin, Nobuyasu Baba, Manuel Rubio, Marika Sarfati
発行年月 2009/03
概要 Th17 cells are implicated in host defence and autoimmune diseases. CD28/B7 co-stimulation is involved in the induction and progression of autoimmune diseases, but its role in controlling murine Th17 cell fate remains to be clarified. We here report that soluble anti-CD28 mAb suppressed the differentiation of anti-CD3-stimulated naïve CD4(+) T cells into IL-17-producing cells. CD28 co-stimulation reduced the frequency of proliferating cells that produce IL-17. We provide evidence for an IL-2 and IFN-gamma-dependent mechanism of CD28-mediated IL-17 suppression. CD28 blockade of Th17 development was correlated with a decrease rather than an increase in the percentage of Foxp3(+) T cells. In APC/T cell co-cultures, mature dendritic cells (DC) were less efficient than immature DC in their ability to support Th17 cell differentiation, while CTLA4-Ig, an agent blocking CD28/B7 and CTLA4/B7 interactions, facilitated both murine and human Th17 differentiation. This study identifies the importance of B7 co-stimulatory molecules in the negative regulation of Th17 development. These unexpected results caution targeting the CD28/B7 pathways in the treatment of human autoimmune diseases.
DOI 10.1371/journal.pone.0005087
PMID 19333372