Sykes M, Sheard M, Sachs D H
Transplantation Biology Section, National Cancer Institute, Bethesda, MD 20892.
J Immunol. 1988 Oct 1;141(7):2282-8.
The opposing problems of graft-vs-host disease (GVHD) and failure of alloengraftment present major obstacles to the application of bone marrow transplantation (BMT) across complete MHC barriers. The addition of syngeneic T-cell-depleted (TCD) bone marrow (BM) to untreated fully allogeneic marrow inocula in lethally irradiated mice has been previously shown to provide protection from GVHD. We have used this model to study the effects of allogeneic T cells on levels of chimerism in recipients of mixed marrow inocula. The results indicate that T cells in allogeneic BM inocula eliminate both coadministered recipient-strain and radioresistant host hematopoietic elements to produce complete allogeneic chimerism without clinical GVHD. To determine the role of GVH reactivity in this phenomenon, we performed similar studies in an F1 into parent combination, in which the genetic potential for GVHD is lacking. The presence of T cells in F1 marrow inocula led to predominant repopulation with F1 lymphocytes in such chimeras, even when coadministered with TCD-recipient-strain BM. These results imply that the ability of allogeneic BM cells removed by T cell depletion to increase levels of allochimerism may be mediated by a population which is distinct from that which produces GVHD. These results may have implications for clinical BM transplantation.
移植物抗宿主病（GVHD）和同种异体植入失败这两个相反的问题是跨越完整主要组织相容性复合体（MHC）屏障进行骨髓移植（BMT）的主要障碍。先前已证明，在接受致死性照射的小鼠中，将同基因T细胞去除（TCD）的骨髓（BM）添加到未经处理的完全异基因骨髓接种物中，可预防GVHD。我们使用该模型研究异基因T细胞对混合骨髓接种物受体中嵌合水平的影响。结果表明，异基因BM接种物中的T细胞消除了共同给药的受体品系和抗辐射宿主造血成分，从而产生了完全异基因嵌合体，且无临床GVHD。为了确定GVH反应性在这一现象中的作用，我们在F1与亲本品系组合中进行了类似研究，其中缺乏发生GVHD的遗传可能性。在这种嵌合体中，F1骨髓接种物中T细胞的存在导致F1淋巴细胞占主导地位的再增殖，即使与TCD受体品系BM共同给药也是如此。这些结果表明，通过T细胞去除的异基因BM细胞增加异源嵌合水平的能力可能由不同于产生GVHD的细胞群体介导。这些结果可能对临床BM移植有影响。
