Induction of immunosuppressive functions of dendritic cells in vivo by CD4+CD25+ regulatory T cells:: Role of B7-H3 expression and antigen presentation

被引:110
作者
Mahnke, Karsten [1 ]
Ring, Sabine [1 ]
Johnson, Theron S. [1 ]
Schallenberg, Sonja [1 ]
Schoenfeld, Kurt [1 ]
Storn, Volker [1 ]
Bedke, Tanja [1 ]
Enk, Alexander H. [1 ]
机构
[1] Univ Heidelberg Hosp, Dept Dermatol, D-69115 Heidelberg, Germany
关键词
antigen presentation; dendritic cells; T cells;
D O I
10.1002/eji.200636841
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Suppressive functions of CD4(+)CD25(+) regulatory T cells (Treg) are mainly studied by their interaction with conventional T cells. However, there is evidence that Treg also interact with antigen-presenting cells (APC), leading to suppression of APC function in in vitro coculture systems. Studying the in vivo distribution of Treg after injection, we found that Treg are located in direct proximity to dendritic cells (DC) and affect their functional maturation status. After contact to Treg, DC up-regulate the inhibitory B7-H3 molecule and display reduced numbers of MHC-peptide complexes, leading to impaired T cell stimulatory function. When Treg-exposed DC were used to immunize animals against antigens, the DC failed to produce a robust immune response as compared to control DC. Thus, these data indicate that Treg are able to inhibit DC activation and produce an inhibitory phenotype of DC. Accordingly, Treg may recruit DC for the amplification of immunosuppression by restraining their maturation in vivo and inducing an immunosuppressive phenotype of DC.
引用
收藏
页码:2117 / 2126
页数:10
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