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【3.9】Masashi Watanabe, Ph.D. (NIH)

RIBS Seminar

Masashi Watanabe, Ph.D.
Experimental Immunology Branch, National Cancer Institute,
National Institutes of Health, USA.

Date: March 9 (Thu) Time: 9:30 –10:30
Place: Research Institute for Biomedical Science,
Tokyo University of Science, Conference Room, 2rd Floor.

Title: Unique roles of TECs, DCs and B cells in Treg repertoire formation.

Abstract: Foxp3+ CD4+ regulatory T cells (Treg) are an essential component in maintenance of immunological tolerance against self. Treg are generated in the thymus by relatively strong TCR recognition of self-peptide-MHCII complex (pMHCII) on antigen presenting cells (APCs). In addition to pMHCII dependent TCR signaling, B7 expression on APC is critical for Treg generation through CD28 co-stimulation. APCs that might be capable of providing such TCR/CD28 signaling to developing thymocytes include thymic epithelial cells (TECs), dendritic cells (DCs) and B cells. To date, however, how each APC contributes to the generation of the Treg repertoire specific for self-antigen under physiological condition is not fully understood. To address this question, we generated B7 conditional knockout mice enabling selective deletion of B7 from each APC type and assessed the effect of this cell type-specific perturbation of APC function for the generation of Treg repertoires with distinct self-antigen specificities by utilizing panel of pMHCII-tetramers.

Tregレパトア形成における胸腺抗原提示細胞種特異的な役割
渡辺 政志 先生

Foxp3+ CD4+ regulatory T cell (Treg)は免疫自己寛容の維持に必須である。Tregは胸腺内で抗原提示細胞が提示する自己抗原ペプチド-MHCII複合体(pMHCII)とTCRの相互作用により比較的強いTCRシグナルを受け取った胸腺細胞から分化すると考えられている。Treg分化にはTCRシグナルの他に抗原提示細胞上に発現するB7と胸腺細胞に発現するCD28の相互作用が重要である。胸腺細胞にTCR/CD28シグナルを提供しうる胸腺内抗原提示細胞は胸腺上皮細胞、樹状細胞、B細胞が考えられる。一方、これら各胸腺抗原提示細胞が生理的条件下でどのように自己抗原特異的Tregのレパトア形成に関与しているかの知見は乏しい。我々は1) B7 conditional KOシステムによる各胸腺抗原提示細胞のB7機能の欠損および、2) pMHCII-tetramerを用いて胸腺内の抗原特異的Tregを検出する手法を組み合わせ、各胸腺抗原提示細がどのように自己抗原特異的Tregレパトア形成に関与するか検討した。

Host: Ryo Abe (Division of Immunology, RIBS)

20170309