Premium
Immunomodulatory effects of cyclosporin A on human peripheral blood dendritic cell subsets
Author(s) -
Tajima Kenichirou,
Amakawa Ryuichi,
Ito Tomoki,
Miyaji Michihiko,
Takebayashi Masashi,
Fukuhara Shirou
Publication year - 2003
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2003.01585.x
Subject(s) - cd11c , biology , immune system , t cell , immunology , dendritic cell , cd40 , microbiology and biotechnology , interleukin 10 , cytotoxic t cell , biochemistry , in vitro , phenotype , gene
Summary Cyclosporin A (CsA) is a potent immuno‐suppressant and is approved for the treatment of various disease conditions. The molecular biological mechanism of CsA has been investigated intensively in T cells and has been shown to involve the intracellular calcineurin pathway. Recently, it was reported that CsA has capacities to affect not only T cells but also antigen‐presenting cells such as B cells and dendritic cells (DCs). DCs are a master regulator of immune responses that have an integral capacity to prime naive T cells. In the present study, we investigated the biological effects of CsA on human peripheral blood DC subsets: CD11c + myeloid and CD11c − lymphoid subsets. CsA inhibited the up‐regulation of co‐stimulatory molecules induced with or without microbial stimuli and CD40L on both CD11c + and CD11c − subsets. In addition, CsA negatively regulated the endocytic activity of CD11c + DC during the immature state. CsA inhibited the interleukin‐12 (IL‐12) production, but augmented the IL‐10 production from the LPS‐stimulated CD11c + subset, whereas CsA reduced the interferon‐α (IFN‐α) production from the CD11c − subset infected with Sendai virus (SV). Both the LPS‐stimulated CD11c + subset and SV‐infected CD11c − subset preferentially induced the development of IFN‐γ‐producing T helper‐type 1 (Th1) cells. Pretreatment of these DC subsets with CsA inhibited the Th1 skewing. These findings suggested a DC‐mediated mechanism of immunosupression by CsA.