Lubin I, Segall H, Erlich P, David M, Marcus H, Fire G, Burakova T, Kulova L, Reisner Y
Department of Membrane Research and Biophysics, Weizmann Institute of Science, Rehovot, Israel.
Transplantation. 1995 Oct 15;60(7):740-7. doi: 10.1097/00007890-199510150-00022.
We have recently shown that lethally irradiated normal strains of mice, radioprotected with SCID bone marrow, can be engrafted with human peripheral blood mononuclear cells (PBMC). We now demonstrate that lethally irradiated Lewis rats can also be radioprotected with a transplant of SCID bone marrow cells, administered 1 day after total body irradiation. Split chimerism was found in PBMC, 30 days after transplantation, with predominance of SCID donor-type cells. The average percentages of CD4 and CD8 T cells, of mouse or rat origin, were < 1%. This chimerism status could be maintained for over 3 months. When human PBMC (300-1000 x 10(6) cells) were transplanted intraperitoneally 1 day after the administration of SCID bone marrow, prompt engraftment of human CD4 and human CD8 T cells, as well as human CD20 B cells, was found in the peritoneum and in internal organ (such as liver, lung, spleen, thymus, and lymph nodes). T cell activation was high: about 50% of the cells expressed HLA-DR and almost all expressed CD45RO. High titers of human Ig (> 1 mg/ml) were initially found after 2 weeks; these levels were similar to those found in the irradiated mouse model and in the SCID model. Likewise, marked human anti-tetanus response, predominantly of the IgG type, was recorded 2 weeks after the immunization, reaching maximal levels at 4 weeks. The triple-chimeric SCID-like rats, which accept as much as 1000 x 10(6) human PBMC, can potentially be used to elicit both antibody responses and T cell responses against specific antigens, with the advantages of a larger animal.
我们最近发现，经致死剂量照射的正常小鼠品系，用SCID骨髓进行辐射防护后，可植入人外周血单个核细胞（PBMC）。我们现在证明，经致死剂量照射的Lewis大鼠也可用SCID骨髓细胞移植进行辐射防护，在全身照射后1天给药。移植后30天，在PBMC中发现了混合嵌合体，以SCID供体型细胞为主。小鼠或大鼠来源的CD4和CD8 T细胞的平均百分比<1%。这种嵌合状态可维持3个月以上。当在给予SCID骨髓后1天经腹腔移植人PBMC（300 - 1000×10⁶个细胞）时，在腹膜和内脏器官（如肝脏、肺、脾脏、胸腺和淋巴结）中发现人CD4和人CD8 T细胞以及人CD20 B细胞迅速植入。T细胞活化程度很高：约50%的细胞表达HLA - DR，几乎所有细胞都表达CD45RO。最初在2周后发现高滴度的人Ig（>1mg/ml）；这些水平与在照射小鼠模型和SCID模型中发现的水平相似。同样，在免疫后2周记录到明显的人抗破伤风反应，主要为IgG型，在4周时达到最高水平。这种能接受多达1000×10⁶个人PBMC的三嵌合SCID样大鼠，有可能用于引发针对特定抗原的抗体反应和T细胞反应，具有较大动物的优势。
