L3T4-positive T cells participate in the induction of graft-vs-host disease in response to minor histocompatibility antigens.

L3T4-positive T cells participate in the induction of graft-vs-host disease in response to minor histocompatibility antigens.
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DOI:
10.4049/jimmunol.139.8.2511
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发表时间:
1987-10
影响因子:
4.4
通讯作者:
B. Hamilton
B. Hamilton
中科院分区:
医学2区
文献类型:
--
作者:
B. Hamilton

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通过使用Lyt-2和L3 T4抗原的单克隆抗体的阴性选择,在三种H-2相容性菌株组合中确定了响应于次要组织相容性抗原(次要HA)而引发移植物抗宿主病(GVHD)的T细胞表型,以检验Lyt-2阳性T细胞单独引发GVHD的假设。启动GVHD所需的T细胞表型在所研究的三种菌株组合中各不相同。Lyt-2+和L3 T4 + LP脾细胞是引起C57 BL/6受体致死性GVHD所必需的。在相互移植中,Lyt-2+而不是L3 T4 + C57 BL/6脾细胞足以在LP受体中引发GVHD。相反,L3 T4+而不是Lyt-2+ B10.D2脾细胞被发现在BALB/c受体中引发GVHD。对次要HA的最佳应答需要Lyt-2+和L3 T4 + T细胞,因为在所研究的所有三种菌株组合中,脾细胞的两个子集的混合物导致比单独的任一子集更严重形式的GVHD。这项研究表明,L3 T4+细胞参与GVHD的启动,以响应轻微的HA。启动GVHD的优势T细胞亚群随测试的特定菌株组合而变化。在移植受体中表达的特异性次要HA、H-2型和可能的供体菌株的非主要组织相容性复合物免疫应答基因似乎决定了起始T细胞的表型。
The phenotype of T cells that initiate graft-vs-host disease (GVHD) in response to minor histocompatibility antigens (minor HA) was determined in three H-2 compatible strain combinations by using negative selection with monoclonal antibodies to Lyt-2 and L3T4 antigens to test the hypothesis that Lyt-2-positive T cells alone initiate GVHD. The phenotype of T cells required to initiate GVHD was different in each of the three strain combinations studied. Both Lyt-2+ and L3T4+ LP spleen cells were necessary to cause lethal GVHD in C57BL/6 recipients. In the reciprocal transplant, Lyt-2+, but not L3T4+ C57BL/6 spleen cells were sufficient to initiate GVHD in LP recipients. In contrast, L3T4+, but not Lyt-2+ B10.D2 spleen cells were found to initiate GVHD in BALB/c recipients. The optimal response to minor HA requires both Lyt-2+ and L3T4+ T cells because a mixture of the two subsets of spleen cells resulted in a more severe form of GVHD than either subset alone in all three strain combinations studied. This study demonstrates that L3T4+ cells participate in the initiation of GVHD in response to minor HA. The dominant T cell subset that initiates GVHD varies with the specific strain combination tested. The specific minor HA expressed in the transplant recipient, the H-2 type, and possibly non-major histocompatibility complex immune response genes of the donor strain appear to determine the phenotype of the initiator T cells.