RATIONALE FOR BONE-MARROW TRANSPLANTATION IN THE TREATMENT OF AUTOIMMUNE-DISEASES
RATIONALE FOR BONE-MARROW TRANSPLANTATION IN THE TREATMENT OF AUTOIMMUNE-DISEASES
复制标题
DOI：
10.1073/pnas.82.8.2483
复制
发表时间：
1985-01-01
影响因子：
11.1
通讯作者：
HAMASHIMA, Y
中科院分区：
文献类型：
--
作者：
IKEHARA, S;GOOD, RA;HAMASHIMA, Y
将C3H/HeN nu/nu （H-2k）小鼠的正常骨髓移植到年轻的MRL/MP-lpr/lpr （MRL/l; H-2k）小鼠（< 1.5月龄）体内，可预防自身免疫性疾病的发生和特特性胸腺异常。对患有自身免疫性疾病和淋巴结病的雌性MRL/1 （bbbb2个月）或雄性BXSB （H-2b）小鼠（9个月）进行致死性照射，然后用年轻BALB/c nu/nu （H-2d）小鼠（< 2个月）的异体骨髓细胞重建，受体在骨髓移植后存活b> 3个月，无移植物vs。宿主反应。组织病理学研究显示，这些小鼠的淋巴结病消失了，所有自身免疫性疾病的证据要么被阻止发展，要么在其发展后被完全纠正。所有异常t细胞功能均恢复正常。新开发的T细胞对骨髓供体型（BALB/c）和宿主型（MRL/l或BXSB）主要组织相容性复合体（MHC）决定因子均具有耐受性。自身免疫易感性小鼠的t细胞功能障碍可能与发生在自身免疫易感性小鼠胸腺的进化变化以及存在于干细胞中的异常有关。来自BALB/c nu/nu供体的正常干细胞可以分化为正常功能的T细胞，即使在胸腺经历了被认为是退化的小鼠中，如本研究中的BXSB或MRL/l小鼠。骨髓移植可能最终被认为是一种治疗人类危及生命的自身免疫性疾病的方法。自身免疫易感性小鼠的t细胞功能障碍以前被认为是发生在这些小鼠胸腺的进化变化，而现在可能被认为是主要存在于自身免疫易感性小鼠的干细胞中的异常。
Transplantation of normal bone marrow from C3H/HeN nu/nu (H-2k) mice into young MRL/MP-lpr/lpr (MRL/l; H-2k) mice (< 1.5 mo.) prevented the development of autoimmune diseases and characteristic thymic abnormalities in the recipient mice. When female MRL/1 (> 2 mo.) or male BXSB (H-2b) mice (9 mo.) with autoimmune diseases and lymphadenopathy were lethally irradiated and then reconstituted with allogeneic bone marrow cells from young BALB/c nu/nu (H-2d) mice (< 2 mo.), the recipients survived for > 3 mo. after the bone marrow transplantation and showed no graft-vs.-host reaction. Histopathological study revealed that lymphadenopathy disappeared and that all evidence of autoimmune disease either was prevented from developing or was completely corrected even after its development in such mice. All abnomal T-cell functions were restored to normal. The newly developed T cells were tolerant of both bone marrow donor-type (BALB/c) and host-type (MRL/l or BXSB) major histocompatibility complex (MHC) determinants. T-cell dysfunction in autoimmune-prone mice can be associated with both the involutionary changes that occur in the thymus of the autoimmune-prone mice and also to abnormalities that reside in the stem cells. Normal stem cells from BALB/c nu/nu donors can differentiate into normal functional T cells even in mice whose thymus had undergone considered involution, as in the case of BXSB or MRL/l mice in the present studies. Marrow transplantation may be a strategy ultimately to be considered as an approach to treatment of life-threatening autoimmune diseases in humans. T-cell dysfunction in autoimmune-prone mice previously attributed to involutionary changes that occur in the thymus of these mice may instead by attributed to abnormalities that basically reside in the stem cells of the autoimmune-prone mice.