Studies on Immunologic Reconstitution after HLA-haplotype Mismatched parental Marrow Transplantation

HLA单倍型错配亲本骨髓移植后免疫重建的研究

• 批准号: 61440043
• 负责人: KONNO Tasuke
• 金额: $ 16万
• 依托单位: TOHOKU UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (A)
• 财政年份: 1986
• 资助国家: 日本
• 起止时间: 1986 至 1987
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61440043/
• 关键词: Bone marrow transplantation; HLA-haplotype; histoincompability; I cell-depleted immunodeficiency; flow cytometry; NK activity; NK活性; 寛容; HLA; リンパ球膜分化抗原; 白血病

A. T cell-depletd, HLA-haplotype mismatched, parental marrow has been usedfor transplant in patients with severe immune deficiency diseases and leukemia. Previously, we succeeded in transplantation of soy bean agglutinin- and sheep red cell rosiesting-fractionated, maternal marrow in apatient with severe combined imunodeficiency (SIDC). Kinetics of immune reconstitution after the bone marrow transplantation (BMT) were investigated in this patient. 1. Cellular immunity recovered relatively rapidly with normal T cell subpopulations and positive delayedtype hyper sensitivity against PPD. Four years later, CD4^+ cells decreased and the ratio of CD4^+/CD8^+ was less than 1.0. Unusual T cells which express CD3 but neither CD4 nor CD8 antigens increased comprising 10 30 % of peripheral T cells. These CD3^+4^-8^SD1 cells, although not identified yet, seemed to correspond to cells which express the <gamma> protein of the T cell receptor but not its <alpha>- and <beta>- chains in association with the CD3 complex. 2. T cells in the patients were shown to be of donor origin but B cells to be of host origin. The reconstitution of humoral immunity was achieved 5 years after BMT, resulting in discontinuation of immunoglobulin replacement. This indicates that HLA haploidentical donor stem cells are able to differentiate and mature to functional T cells which can cooperate with host B cells for antibody production. 3. Little NK actiivty has been demonstrated during the course after BNT in the patient. Leu 7 cells were found soon after engraftment but Leu 11 cells in appeared first 5 years later.B. Last 2 years, two other patients underwent HLA-mismatched BMT; One with SCID succumbed to severe infection after the treatemnu and the other with Fancom's anemia too early to be evaluated.C. Five patients with various types of leukemia underwent HLA-mached alogeneic BMT and in all cases, hematologic and immunologic functions have been reconstituted.

A. T细胞耗竭、HLA单倍型不匹配的亲本骨髓已被用于严重免疫缺陷疾病和白血病患者的移植。以前，我们成功地将大豆凝集素和绵羊红细胞玫瑰红细胞分离的母体骨髓移植给患有严重联合免疫缺陷症（SIDC）的患者。本文观察了该患者骨髓移植后免疫重建的动力学。1.细胞免疫恢复相对较快，T细胞亚群正常，PPD迟发型超敏反应阳性。4年后，CD 4 ^+细胞减少，CD 4 ^+/CD 8 ^+比值小于1.0。不寻常的T细胞，表达CD 3，但既不CD 4也不CD 8抗原增加，包括10 - 30%的外周血T细胞。这些CD 3 ^+4^-8 ^SD 1细胞尽管尚未鉴定，但似乎对应于<gamma>表达T细胞受体蛋白但不表达<alpha><beta>与CD 3复合物相关的其-和-链的细胞。2.患者的T细胞显示为供体来源，但B细胞为宿主来源。骨髓移植后5年体液免疫重建，导致免疫球蛋白替代治疗中断。这表明HLA半相合供体干细胞能够分化和成熟为功能性T细胞，其可以与宿主B细胞合作用于抗体产生。3.在患者BNT后的过程中，几乎没有NK活性被证明。移植后不久即发现Leu 7细胞，而Leu 11细胞在移植后5年才出现。最近2年，另外2例患者接受了HLA不匹配的骨髓移植; 1例SCID患者在移植后死于严重感染，另1例Fancom贫血过早，无法评估。5例不同类型白血病患者接受HLA配型的同种异体骨髓移植，均获得了造血和免疫功能的重建。

项目成果

Tsuchiya,S etal: Tohoku Journal experimental Medicine. 150. 455-465 (1986)

Tsuchiya，S etal：东北实验医学杂志。

今野 多助: Immunohematology-免疫と血液-. 9. 139-143 (1987)

Tasuke Konno：免疫血液学-免疫和血液-。9. 139-143 (1987)

Eibl.MM,Rosen FS (editors); Konno,T.: "Primary Immunodeficiency Disease; OMM-1,(MO-1)/LFA-1 deficiency in a Japanese infant with recurrent infection" 378;315-318 (1986)

Eibl.MM，Rosen FS（编辑）；

Tsuhciya, S et al: "Adaptation of a human monocytic leukemia cell line (THP-1) in a protein-free chemically defined medium" Tohku Journal experimental Medicine. 150. 455-465 (1986)

Tsuhciya, S 等人：“人单核细胞白血病细胞系 (THP-1) 在无蛋白质化学成分确定的培养基中的适应”Tohku Journal Experimental Medicine。

今野 多助 他: 日本臨床免疫学会々誌. (1988)

Tasuke Konno 等人：日本临床免疫学会杂志 (1988)。