Expansion of CD4+ CD25+ Foxp3+ T cells by bone marrow-derived dendritic cells

Abstract

Dendritic cells (DCs) are the most important antigen-presenting cells of the immune system and have a crucial role in T-lymphocyte activation and adaptive immunity initiation. However, DCs have also been implicated in maintaining immunological tolerance. In this study, we evaluated changes in the CD4+ CD25+ Foxp3+ T-cell population after co-culture of lymph node cells from BALB/c mice with syngeneic bone marrow-derived DCs. Our results showed an increase in CD4+ CD25 + Foxp3+ T cells after co-culture which occurred regardless of the activation state of DCs and the presence of allogeneic apoptotic cells; however, it was greater when DCs were immature and were pulsed with the alloantigen. Interestingly, syngeneic apoptotic thymocytes were not as efficient as allogeneic apoptotic cells in expanding the CD4+ CD25+ Foxp3+ T-cell population. In all experimental settings, DCs produced high amounts of transforming growth factor (TGF)-β. The presence of allogeneic apoptotic cells induced interleukin (IL)-2 production in immature and mature DC cultures. This cytokine was also detected in the supernatants under all experimental conditions and enhanced when immature DCs were pulsed with the alloantigen. CD4+ CD25+ Foxp3 + T-cell expansion during co-culture of lymph node cells with DCs strongly suggested that the presence of alloantigen enhanced the number of regulatory T cells (Tregs) in vitro. Our data also suggest a role for both TGF-β and IL-2 in the augmentation of the CD4+ CD25+ Foxp3+ population. © 2008 Blackwell Publishing Ltd.