Bone marrow transplantation across major histocompatability barriers in mice. III. Treatment of donor grafts with monoclonal antibodies directed against Lyt determinants.
Bone marrow transplantation across major histocompatability barriers in mice. III. Treatment of donor grafts with monoclonal antibodies directed against Lyt determinants.
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DOI：
10.4049/jimmunol.128.2.871
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发表时间：
1982-02
影响因子：
4.4
通讯作者：
D. Vallera;C. Soderling;J. H. Kersey
中科院分区：
文献类型：
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作者：
D. Vallera;C. Soderling;J. H. Kersey
我们研究了在一个系统中，骨髓移植跨越主要组织相容性屏障，从小鼠供体移植物中消除T细胞的效果。BALB/c骨髓（作为造血干细胞来源）与等体积的脾细胞（作为GVHD促进细胞来源）组合，在注射到C57 BL/6全身照射受体之前，用单克隆抗Lyt-1.2或Lyt-2.2加吸收的兔补体体外预处理。在CML测定中测定抗Lyt单克隆抗体的功能活性。用抗Lyt-1.2加C处理没有任何抗干细胞活性，如通过CFU-S测定所测量的，并且保护受体免于致死性GVHD的发作。用Lyt-2.2加C处理也没有减少CFU-S;然而，接受处理的骨髓的小鼠确实发展GVHD，并且在2个月时全部死亡，与未处理的对照小鼠一样。存活的“抗Lyt-1.2 + C嵌合体”在其外周血中表现出高百分比的供体单核细胞。当用单克隆抗Lyt-1.1加C处理C3 H/HeN供体BMS并注射到C57 BL/6受体中时，获得了类似的结果。这些发现表明，针对与Thy-1无关的决定簇的单克隆抗体可以在C存在的情况下消除T细胞，并成功地保护移植小鼠免受致死性GVHD。他们还表明，这些抗Lyt抗体可能是确定有助于GVHD发展的T细胞亚群的有用工具。
We studied the effect of eliminating T cells from donor grafts of mice in a system in which bone marrow was transplanted across major histocompatibility barriers. BALB/c bone marrow (added as a source of hematopoietic stem cells) combined with equal volumes of spleen cells (added as a source of GVHD-promoting cells) was pretreated in vitro with monoclonal anti-Lyt-1.2 or Lyt-2.2 plus absorbed rabbit complement before injection into C57BL/6 total-body-irradiated recipients. Functional activity of anti-Lyt monoclonal antibodies was determined in CML assay. Treatment with anti Lyt-1.2 plus C did not have any anti-stem cell activity, as measured by CFU-S assay, and protected recipients from the onset of lethal GVHD. Treatment with Lyt-2.2 plus C also did not reduce CFU-S; however, mice receiving treated marrow did develop GVHD and were all dead by 2 mo, as were untreated control mice. Surviving "anti-Lyt-1.2 + C chimeras" demonstrated a high percentage of donor mononuclear cells in their peripheral blood. Similar results were obtained when C3H/HeN donor BMS was treated with monoclonal anti-Lyt-1.1 plus C and injected into C57BL/6 recipients. These findings show that monoclonal antibodies directed against determinants unrelated to Thy-1 can eliminate T cells in the presence of C and successfully protect transplanted mice from lethal GVHD. They also suggest that these anti-Lyt antibodies may be useful tools in determining subpopulations of T cells that contribute to the development of GVHD.