Antigen-Specific Suppression of a Primed Immune Response by Dendritic Cells Mediated by Regulatory T cells Secreting Interleukin-10

Speaker: 蕭玉翎

Commentator: 葉才明 老師

Time: Room 601, 2003/3/19

Abstract:

Antigen-specific suppression of a previously primed immune response may form the foundation of new treatment modalities directed against autoimmunity. Previous studies have shown thatNF-kB family member particularly RelB plays an essential role in controlling the pathway for myeloid dendritic cells (DCs) maturation¹. BAY 11-7082 (BAY) has been shown to block TNFa-stimulated NF-kB translocation through inhibition of IkBa phosphorylation². In addition, RelB regulates B cell APC function through regulation of CD40 and MHC molecule expression³. In this paper, the authors show that antigen-exposed myeloid DCs in which RelB function is inhibited lack cell surface CD40 expression, prevent priming of immunity, and suppress a previously primed immune response. In vitro-derived immature bone marrow derived DCs (BMDCs) share some characteristics of the BAY-treated BMDCs, including modest induction of tolerance.⁴ DCs generated from RelB-deficient mice and CD40-deficient mice similarly conferred suppression. DC tolerogenicity has been associated with NF-kB-dependent transcription of costimulatory genes through impaired nuclear translocation. CD40 deficiency as opposed to DC immaturity determines the consequences of presentation of antigen by myeloid DCs. Regulatory CD4 T cells induced by the DCs transfer antigen-specific “infectious” tolerance to primed recipients in an IL-10-dependent fashion. These observations are significant for autoimmune immunotherapy and also suggest a mechanism by which peripheral tolerance might be constitutively maintained by myeloid DCs in which RelB and CD40 are either suppressed or deficient.

References:

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2.      Pierce, J. W., et al. Novel inhibitors of cytokine-induced IkBa phosphorylation and endothelial cell adhesion molecule expression show anti-inflammatory effects in vivo. J. Biol. Chem. 272, 21096-21103. (1997)

3.      O’Sullivan, B. J., et al. RelB nuclear translocation regulates B cell MHC molecule, CD40 expression, and antigen-presenting cell function. Proc. Natl. Acad. Sci. USA 97, 11421-11426. (2000)

4.      Martin, E., et al. Antigen-specific suppression of a primed immune response by dendritic cells mediated by regulatory T cells secreting interleukin-10. Immunity 18, 155-167. (2003)