PMID- 20081875 OWN - NLM STAT- MEDLINE DCOM- 20100308 LR - 20211020 IS - 2042-0226 (Electronic) IS - 1672-7681 (Print) IS - 1672-7681 (Linking) VI - 7 IP - 1 DP - 2010 Jan TI - CD40-activated B cells are more potent than immature dendritic cells to induce and expand CD4(+) regulatory T cells. PG - 44-50 LID - 10.1038/cmi.2009.103 [doi] AB - 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. FAU - Zheng, Jian AU - Zheng J AD - Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, University of Hong Kong, Hong Kong, China. FAU - Liu, Yinping AU - Liu Y FAU - Lau, Yu-Lung AU - Lau YL FAU - Tu, Wenwei AU - Tu W LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - China TA - Cell Mol Immunol JT - Cellular & molecular immunology JID - 101242872 RN - 0 (CD40 Antigens) RN - 0 (Interleukin-2 Receptor alpha Subunit) SB - IM MH - B-Lymphocytes/*immunology MH - CD40 Antigens/*immunology MH - *Cell Communication MH - *Cell Differentiation MH - Coculture Techniques MH - Dendritic Cells/cytology/*immunology MH - Humans MH - Interleukin-2 Receptor alpha Subunit/immunology MH - T-Lymphocytes, Regulatory/cytology/*immunology PMC - PMC4003254 EDAT- 2010/01/19 06:00 MHDA- 2010/03/10 06:00 PMCR- 2010/01/01 CRDT- 2010/01/19 06:00 PHST- 2010/01/19 06:00 [entrez] PHST- 2010/01/19 06:00 [pubmed] PHST- 2010/03/10 06:00 [medline] PHST- 2010/01/01 00:00 [pmc-release] AID - cmi2009103 [pii] AID - 10.1038/cmi.2009.103 [doi] PST - ppublish SO - Cell Mol Immunol. 2010 Jan;7(1):44-50. doi: 10.1038/cmi.2009.103.