Iwai H, Yasumizu R, Sugiura K, Inaba M, Kumazawa T, Good R A, Ikehara S
1st Department of Pathology, Kansai Medical College, Osaka, Japan.
Immunology. 1987 Nov;62(3):457-62.
We have established a new method for pancreatic allografts in mice by combining pancreatic transplantation with allogeneic bone marrow transplantation. In this approach, we first transplanted bone marrow to induce tolerance to both donor-type and host-type major histocompatibility complex (MHC) determinants. Pancreatic tissue from the same mouse strain as bone marrow donor was then grafted under the renal capsule. Acceptance of the grafts was confirmed by histopathological and immunohistochemical techniques. BALB/c mice reconstituted with C57BL/6J bone marrow cells accepted pancreatic tissue from both bone marrow donor (C57BL/6J)-type and host (BALB/c)-type mice. An immunohistochemical study revealed the presence of functional islets under the renal capsules. Assays for both mixed lymphocyte reaction (MLR) and induction of cytotoxic T lymphocytes indicated that the newly developed T cells are tolerant of both donor (stem cell)-type and host-type MHC determinants. By contrast, the T cells of these chimeras showed a significant responsiveness to third party MHC determinants. These findings suggest that pancreatic allografts combined with bone marrow transplantation may become a viable strategy for the treatment of patients with diabetes or patients who have undergone pancreatectomy.
我们通过将胰腺移植与同种异体骨髓移植相结合，建立了一种用于小鼠胰腺同种异体移植的新方法。在这种方法中，我们首先移植骨髓以诱导对供体型和宿主型主要组织相容性复合体（MHC）决定簇的耐受性。然后将来自与骨髓供体相同小鼠品系的胰腺组织移植到肾被膜下。通过组织病理学和免疫组织化学技术确认了移植物的接受情况。用C57BL/6J骨髓细胞重建的BALB/c小鼠接受了来自骨髓供体（C57BL/6J）型和宿主（BALB/c）型小鼠的胰腺组织。免疫组织化学研究显示肾被膜下存在功能性胰岛。混合淋巴细胞反应（MLR）和细胞毒性T淋巴细胞诱导试验均表明，新产生的T细胞对供体（干细胞）型和宿主型MHC决定簇均具有耐受性。相比之下，这些嵌合体的T细胞对第三方MHC决定簇表现出显著的反应性。这些发现表明，胰腺同种异体移植联合骨髓移植可能成为治疗糖尿病患者或接受胰腺切除术患者的可行策略。
