Complete blockade of B7 family-mediated costimulation is necessary to induce human alloantigen-specific anergy: A method to ameliorate graft-versus-host disease and extend the donor pool
Complete blockade of B7 family-mediated costimulation is necessary to induce human alloantigen-specific anergy: A method to ameliorate graft-versus-host disease and extend the donor pool
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DOI：
10.1182/blood.v87.11.4887.bloodjournal87114887
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发表时间：
1996-06-01
期刊：
影响因子：
20.3
通讯作者：
Nadler, LM
中科院分区：
文献类型：
--
作者：
Gribben, JG;Guinan, EC;Nadler, LM
移植物抗宿主病（GVHD）是由识别宿主同种异体抗原的过继转移的供体T细胞引发的。尽管在混合白细胞反应中供体T细胞对宿主同种异体抗原的增殖的缺乏并不能预测免于GVHD，但同种异体反应性前体辅助T淋巴细胞（pHTL）的频率是预测性的。完全阻断B7家族介导的共刺激，但不阻断主要组织相容性复合体的识别或粘附，通过将细胞因子的产生降低到常见γ链信号传导所需的阈值水平以下来诱导宿主同种异体抗原特异性无能。与之相关的同种异体反应性pHTL频率降低到GVHD预测值以下，而不消耗非同种异体特异性T细胞或造血祖细胞，这使我们开始进行单倍型异基因骨髓移植的人体临床试验。(C)1996年，美国血液学会。
Graft-versus-host disease (GVHD) is initiated by adoptively transferred donor T cells that recognize host alloantigens. Whereas the absence of donor T-cell proliferation to host alloantigens in a mixed-leukocyte reaction does not predict freedom from GVHD, the frequency of alloreactive precursor helper T lymphocytes (pHTL) is predictive. Complete blockade of B7 family-mediated costimulation, but not of major histocompatibility complex recognition or adhesion, induces host alloantigen-specific anergy by reducing cytokine production below threshold levels necessary for common gamma-chain signaling. The associated reduction of alloreactive pHTL frequency below that predictive for GVHD, without depletion of either nonallospecific T cells or hematopoietic progenitors, has led us to embark upon human clinical trials of haplomismatched allogeneic bone marrow transplantation. (C) 1996 by The American Society of Hematology.