Gribben J G, Guinan E C, Boussiotis V A, Ke X Y, Linsley L, Sieff C, Gray G S, Freeman G J, Nadler L M
Division of Hematologic Malignancies, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
Blood. 1996 Jun 1;87(11):4887-93.
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 87 family-mediated costimulation, but not of major histocompatibility complex recognition or adhesion, induces host alloantigenic-specific energy 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.
移植物抗宿主病（GVHD）由过继转移的识别宿主同种异体抗原的供体T细胞引发。虽然在混合淋巴细胞反应中供体T细胞对宿主同种异体抗原无增殖反应并不能预测不会发生GVHD，但同种异体反应性前体辅助性T淋巴细胞（pHTL）的频率具有预测性。完全阻断87家族介导的共刺激，但不阻断主要组织相容性复合体识别或黏附，通过将细胞因子产生降低到共同γ链信号传导所需的阈值水平以下，诱导宿主同种异体抗原特异性无能。同种异体反应性pHTL频率的相关降低低于预测GVHD的水平，而不消耗非同种特异性T细胞或造血祖细胞，这促使我们开展单倍体匹配的异基因骨髓移植的人体临床试验。
