デスモグレイン3(Dsg3)特異的T細胞(H1T細胞)を用いて, 末梢性免疫寛容機構の同定及び解析が可能な2つの実験系を確立した。ヌードマウスへの胸腺移植により胸腺でのみDag3を欠損するマウスを作成し, H1-tgマウスの骨髄を移植する。するとDsg3欠損胸腺で成熟したH1T細胞がDsg3の存在する末梢組織中で消失する。他方, H1-Dsg3-/-マウスの末梢組織中のH1T細胞を野生型マウスに養子移入すると, 移入された細胞は分裂後に消失する。これらを応用し, 末梢性免疫寛容機構が皮膚リンパ節での抗原提示から始まること, 分裂と消失の過程に分けられ, 複数の細胞群から成立していることを明らかにした。
Utilizing desmoglein3 (Dsg3)-specific T cells (H1 T cells), two experimental models were established for clarification and analysis of peripheral immune tolerance mechanism. In the first model, we made mice, which lack Dsg3 only in the thymus by applying thymus transplantation into Nude mice, and then performed bone marrow transplantation to these mice from H1-tg mice. In these mice, H1 T cells matured in Dsg3 deficient thymus, and then, disappeared in Dsg3 expressing periphery. In the other model, H1 T cells existing in the periphery of H1-Dsg3-/-mice were adoptively transferred into WT mice. In these WT mice, H1 T cells disappeared after proliferation. Taking advantage of these models, we clarified that peripheral immune tolerance mechanism is initiated by antigen presentation to H1 T cells in skin-draining lymph node, and divided into proliferation phase and disappearance phase, orchestrated by some kinds of cell populations.
|
