Immune Netw.  2016 Feb;16(1):13-25. 10.4110/in.2016.16.1.13.

Induction of CD4+ Regulatory and Polarized Effector/helper T Cells by Dendritic Cells

• Lutz MB

• KMID: 2154807
• DOI: http://doi.org/10.4110/in.2016.16.1.13

Abstract

Dendritic cells (DCs) are considered to play major roles during the induction of T cell immune responses as well as the maintenance of T cell tolerance. Naive CD4+ T cells have been shown to respond with high plasticity to signals inducing their polarization into effector/helper or regulatory T cells. Data obtained from in vitro generated bone-marrow (BM)-derived DCs as well as genetic mouse models revealed an important but not exclusive role of DCs in shaping CD4+ T cell responses. Besides the specialization of some conventional DC subsets for the induction of polarized immunity, also the maturation stage, activation of specialized transcription factors and the cytokine production of DCs have major impact on CD4+ T cells. Since in vitro generated BM-DCs show a high diversity to shape CD4+ T cells and their high similarity to monocyte-derived DCs in vivo, this review reports data mainly on BM-DCs in this process and only touches the roles of transcription factors or of DC subsets, which have been discussed elsewhere. Here, recent findings on 1) the conversion of naive into anergic and further into Foxp3- regulatory T cells (Treg) by immature DCs, 2) the role of RelB in steady state migratory DCs (ssmDCs) for conversion of naive T cells into Foxp3+ Treg, 3) the DC maturation signature for polarized Th2 cell induction and 4) the DC source of IL-12 for Th1 induction are discussed.

Keyword

Dendritic cells; CD4+ T cells; Polarization; Regulatory T cells; Anergy

MeSH Terms

Animals
Dendritic Cells*
Interleukin-12
Mice
Plastics
T-Lymphocytes*
T-Lymphocytes, Regulatory
Th2 Cells
Transcription Factors
Interleukin-12
Plastics
Transcription Factors

Figure

• 

  Figure 1 Induction of CD4+ T cell anergy, Treg subsets and polarized Th1/Th2 responses by DC can be directed by their maturation stages and cytokines. Immature DCs induce antigen-specific T cell anergy in naive T cells in the absence of TGF-β, but induce Foxp3+ iTregs when TGF-β is present. A second stimulation of non-regulatory anergized T cells by immature DCs generates regulatory IL-10+ Tr1 cells. A similar T cell phenotype of regulatory IL-10+ Tr1 is generated by repetitive stimulation with semi-mature BM-DCs generated by maturation with TNF or T. brucei VSG antigens characterized by a lack of cytokine production. A single stimulation with these DCs in the absence of TGF-β and IL-12 induces a Th2 phenotype that is lost upon repetitive stimulation. In vivo steady state migratory DCs (ssmDCs) resemble TNF-matured BM-DCs but capture TGF-β on their surface, thereby inducing naive T cell conversion into Foxp3+ iTreg specific for self-antigens. DCs matured with high doses of LPS or CgG oligonucleotides reach a full maturation stage characterized by cytokine release including IL-12p70 that leads to Th1 induction.

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