Thesis or Dissertation マウス同種異系臍帯血移植による 機能的獲得免疫反応の構築

前田, 浩志

pp.1 - 26 , 2016-03-23
Using a murine model, we investigated whether allogeneic umbilical cord blood cell (UCBC) transplantation facilitates immune reconstitution with functional maturity in comparison with bone marrow cell (BMC) transplantation. UCBCs and BMCs prepared from green fluorescent protein (GFP)-transgenic C57BL/6 (H-2b) mice were transferred into BALB/c (H-2d) mice that had been subjected to lethal total body X-ray irradiation. Although UCBC-transplanted mice showed poorer survival than BMC-transplanted mice for the same number of transplanted cells, increasing the number of transplanted UCBCs improved survival with an increase of donor-derived GFP+ cell engraftment. Flow cytometric analysis revealed development of GFP+ immune cells of donor origin, including T cells, B cells, monocytes, and granulocytes, in the peripheral blood of both sets of recipient mice. Furthermore, the functional maturity of T and B cells involved in adaptive immunity following allogeneic UCBC- and BMC-transplantation was assessed in T- and B-deficient RAG2-/- BALB/c mice. Both sets of recipients showed complete rejection of third-party C3H (H-2k) skin grafts and antibody responses to the T cell-dependent antigen, 2,4,6-trinitrophenyl-keyhole limpet hemocyanin, with immunoglobulin class switching. These results suggest that UCBCs have essentially the same ability as BMCs to reconstitute a functional adaptive immune system, even in an allogeneic environment.

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