Role of dendritic cell maturity/costimulation for generation, homeostasis, and suppressive activity of regulatory T cells

Abstract

Tolerogenicity of dendritic cells (DCs) has initially been attributed exclusively to immature/resting stages, while mature/activated DCs were considered strictly immunogenic. Later, all different subsets among the myeloid/conventional DCs and plasmacytoid DCs have been shown to bear tolerogenic potential, so that tolerogenicity could not be attributed to a specific subset. Immunosuppressive treatments of immature DC subsets could prevent re-programming into mature DCs or upregulated inhibitory surface markers or cytokines. Furthermore, the different T cell tolerance mechanisms anergy, deletion, immune deviation, and suppression require different quantities and qualities of costimulation by DCs. Since expansion of regulatory T cells (Tregs) has been shown to be promoted best by fully mature DCs the role of CD80/B7-1 and CD86/B7-2 as major costimulatory molecules for Treg biology is under debate. In this review, we discuss the role of these and other costimulatory molecules on myeloid DCs and their ligands CD28 and CD152/CTLA-4 on Tregs for peripheral conversion from naive CD4+ T cells into the major subsets of Foxp3+ Tregs and Foxp3− IL-10+ regulatory type-1 T cells (Tr1) or Tr1-like cells and their role for peripheral maintenance in the steady state and after activation.

Allogeneic Mature Human Dendritic Cells Generate Superior Alloreactive Regulatory T Cells in the Presence of IL-15

“…The stimulatory capacity of mature moDCs was also observed for skin-derived DCs and indicates that DCs in vivo also may be important APCs for Treg expansion and survival in the periphery (68). This finding may also explain the observation that a simultaneous influx of both Ag-specific effector T cells and Tregs is observed after s.c. purified protein derivate injection (69).…”

Preparation of Complexes between Ovalbumin Nanoparticles and Retinoic Acid for Efficient Induction of Tolerogenic Dendritic Cells

“…In the semimature state of DCs, presentation of antigen peptides via MHC class II is somewhat activated while expression of costimulatory receptors CD80/86 is kept as low as immature DCs. 7,8,25,26 As shown in Fig. 6 A, DC 2.4 treated with OVA/RA NPs showed slightly higher expression of MHC class II than other control groups.…”

Tolerogenic dendritic cells and their applications in transplantation

“…64 In the immune tolerance model induced by apoptotic cell administration, tol-DCs promoted the expansion of Tregs via PD-L1 expression on their surface, and Tregs facilitated maintenance of a tolerogenic state by tol-DCs via IL-10 and TGF-b. 65 66 These findings highlight that reciprocal interactions between tol-DCs and Tregs are essential for the induction and maintenance of immune tolerance.…”