CD28 co-stimulation down regulates Th17 development

PLoS One. 2009;4(3):e5087. doi: 10.1371/journal.pone.0005087. Epub 2009 Mar 31.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B7-1 Antigen / metabolism*
  • CD28 Antigens / metabolism*
  • CD4-Positive T-Lymphocytes / cytology*
  • Coculture Techniques
  • Dendritic Cells
  • Down-Regulation / physiology
  • Humans
  • Interferon-gamma
  • Interleukin-17 / biosynthesis*
  • Interleukin-2
  • Lymphocyte Activation*
  • Mice
  • T-Lymphocyte Subsets


  • B7-1 Antigen
  • CD28 Antigens
  • Interleukin-17
  • Interleukin-2
  • Interferon-gamma