並列タイトル等タイプ1免疫誘導型樹状細胞は結核菌に対して強力な免疫原性を有する
タイトル（掲載誌）The International Journal of Tuberculosis and Lung Disease
一般注記doctoral
医学系研究科
OBJECTIVE: Application of immunotherapy using dendritic cells (DCs) is considered an effective treatment strategy against persistent Mycobacterium tuberculosis infection. With the goal of developing improved therapeutic vaccination strategies for patients with tuberculosis (TB), we tested the ability of ex vivo-generated DCs to induce an effective TB antigen-specific type-1 immune response.METHODS: Monocyte-derived DCs from TB patients were induced to mature using a “standard” cytokine cocktail (IL-1β, TNF-α, IL-6, and PGE2) or a type 1-polarized DC (DC1) cocktail (IL-1β, TNF-α, IFN-α, IFN-γ, and polyinosinic:polycytidylic acid), and were loaded with the established TB antigen 6-kDa early secretory antigenic target protein (ESAT-6).RESULTS: Although DC1s from TB patients expressed the same levels of multiple co-stimulatory molecules (CD83, CD86, CD80, CD11c, and CD40) as the standard DCs (sDCs), DC1s secreted substantially higher levels of IL-12p70. Furthermore, when DCs pulsed with or without ESAT-6 were cultured with lymphocytes from the same patients, DC1s induced much higher numbers of ESAT-6-specific IFN-γ-producing T cells than sDCs, as manifested by their superior induction of natural killer cells activation and antigen-independent suppression of regulatory T cells.CONCLUSION: TB antigen-loaded DC1s are potent inducers of antigen-specific T cells, which could be used to develop improved immunotherapies of TB.
DOIinfo:doi/10.5588/ijtld.16.0371
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