2009年11月
Induction of Cross-Priming of Naive CD8(+) T Lymphocytes by Recombinant Bacillus Calmette-Guerin That Secretes Heat Shock Protein 70-Major Membrane Protein-II Fusion Protein
JOURNAL OF IMMUNOLOGY
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- 巻
- 183
- 号
- 10
- 開始ページ
- 6561
- 終了ページ
- 6568
- 記述言語
- 英語
- 掲載種別
- 研究論文(学術雑誌)
- DOI
- 10.4049/jimmunol.0803857
- 出版者・発行元
- AMER ASSOC IMMUNOLOGISTS
Because Mycobacterium bovis bacillus Calmette-Guerin (BCG) unconvincingly activates human naive CD8(+) T cells, a rBCG (BCG-70M) that secretes a fusion protein comprising BCG-derived heat shock protein (HSP)70 and Mycobacterium leprae-derived major membrane protein (MMP)-II, one of the immunodominant Ags of M. leprae, was newly constructed to potentiate the ability of activating naive CD8(+) T cells through dendritic cells (DC). BCG-70M secreted HSP70-MMP-II fusion protein in vitro, which stimulated DC to produce IL-12p70 through TLR2. BCG-70M-infected DC activated not only memory and naive CD8(+) T cells, but also CD4(+) T cells of both types to produce IFN-gamma. The activation of these naive T cells by BCG-70M was dependent on the MHC and CD86 molecules on BCG-70M-infected DC, and was significantly inhibited by pretreatment of DC with chloroquine. Both brefeldin A and lactacystin significantly inhibited the activation of naive CD8(+) T cells by BCG-70M through DC. Thus, the CD8(+) T cell activation may be induced by cross-presentation of Ags through a TAP- and proteosome-dependent cytosolic pathway. When naive CD8(+) T cells were stimulated by BCG-70M-infected DC in the presence of naive CD4(+) T cells, CD62L(low)CD8(+) T cells and perforin-producing CD8(+) T cells were efficiently produced. MMP-II-reactive CD4(+) and CD8(+) memory T cells were efficiently produced in C57BL/6 mice by infection with BCG-70M. These results indicate that BCG-70M activated DC, CD4(+) T cells, and CD8(+) T cells, and the combination of HSP70 and MMP-II may be useful for inducing better T cell activation. The Journal of Immunology, 2009, 183: 6561-6568.
- リンク情報
- ID情報
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- DOI : 10.4049/jimmunol.0803857
- ISSN : 0022-1767
- PubMed ID : 19846882
- Web of Science ID : WOS:000271765700060