CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD4(+) regulatory T cells

Cell Mol Immunol. 2010 Jan;7(1):44-50. doi: 10.1038/cmi.2009.103.

Abstract

CD4(+) regulatory T cells (Tregs) play an important role in maintaining immune tolerance by suppressing pathologic immune responses. The generation of large numbers of antigen-specific Tregs ex vivo is critical for the development of clinical immunotherapy based on the adoptive transfer of Tregs. Both CD40-activated B cells (CD40-B) and immature dendritic cells (imDCs) have been used as professional antigen-presenting cells (APCs) to generate antigen-specific Tregs. However, the efficiencies of CD40-B and imDCs to generate CD4(+) Tregs have not been compared directly and the mechanism driving the generation of these Tregs remains largely unknown. In this study, we found that CD40-B exhibited mature phenotypes and were more able to induce and expand CD4(high)CD25(+) Tregs than imDCs. Moreover, Tregs induced by CD40-B had greater suppressive capacity than those induced by imDCs. The generation of CD4(high)CD25(+) Tregs by CD40-B and imDCs is cell-cell contact dependent and partially relies on the expression of human leukocyte antigen (HLA)-DR and CD80/86. Differences in CD4(high)CD25(+) Treg generation efficiency were largely explained by the production of endogenous IL-2 by CD40-B. Our results suggest that CD40-B is better able to generate large numbers of antigen-specific Tregs than imDCs. Additionally, using CD40-B to generate Tregs may accelerate the clinical use of Treg-based immunotherapy in the treatment of allograft rejection, graft versus host disease (GVHD) and autoimmune diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • B-Lymphocytes / immunology*
  • CD40 Antigens / immunology*
  • Cell Communication*
  • Cell Differentiation*
  • Coculture Techniques
  • Dendritic Cells / cytology
  • Dendritic Cells / immunology*
  • Humans
  • Interleukin-2 Receptor alpha Subunit / immunology
  • T-Lymphocytes, Regulatory / cytology
  • T-Lymphocytes, Regulatory / immunology*

Substances

  • CD40 Antigens
  • Interleukin-2 Receptor alpha Subunit