Section of Transplantation Immunology, Department of Stem Cell Transplantation and Cellular Therapy, University of Texas M.D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA.
Biol Blood Marrow Transplant. 2010 Mar;16(3):311-9. doi: 10.1016/j.bbmt.2009.12.002. Epub 2009 Dec 16.
Allogeneic bone marrow transplantation (BMT) is an effective therapy for hematologic malignancies. However graft-versus-host disease (GVHD) is a major limiting factor for a successful patient outcome. GVHD is a result of alloimmune responses of donor T lymphocytes attacking the recipient's cells and tissues. Chemokine receptor CCR5 plays a role in solid organ allograft rejection and mediates murine GVHD pathogenesis. Herein, we report that infiltrating lymphocytes in the skin of human acute GVHD (aGVHD) samples are predominantly CCR5(+) T cells. In addition, we characterized the features of the CCR5 expression on alloreactive T lymphocytes. We found that the CCR5(+) population exhibits the characteristics of the activated effector T cell phenotype. CCR5 expression is upregulated upon allogenic stimulation, and CCR5(+) cells are proliferating with coexpression of T cell activation markers. Furthermore, the activated T cells producing inflammatory cytokine tumor necrosis factor (TNF)alpha, interleukin (IL)-2, or interferon (IFN)-gamma, are positive for CCR5. Thus, CCR5 is a marker for GVHD effector cells and CCR5(+) T cells are active participants in the pathogenesis of human aGVHD.
异基因骨髓移植（BMT）是治疗血液系统恶性肿瘤的有效方法。然而，移植物抗宿主病（GVHD）是影响患者预后的主要限制因素。GVHD 是供体 T 淋巴细胞的同种免疫反应攻击受者细胞和组织的结果。趋化因子受体 CCR5 在实体器官同种异体移植排斥和介导小鼠 GVHD 发病机制中起作用。在此，我们报告称，人类急性移植物抗宿主病（aGVHD）样本皮肤中的浸润淋巴细胞主要是 CCR5(+)T 细胞。此外，我们还对同种反应性 T 淋巴细胞的 CCR5 表达特征进行了描述。我们发现，CCR5(+)群体表现出激活的效应 T 细胞表型的特征。在同种刺激下，CCR5 表达上调，并且 CCR5(+)细胞增殖，同时表达 T 细胞激活标志物。此外，产生炎症细胞因子肿瘤坏死因子（TNF）α、白细胞介素（IL）-2 或干扰素（IFN）-γ的激活 T 细胞对 CCR5 呈阳性。因此，CCR5 是 GVHD 效应细胞的标志物，CCR5(+)T 细胞是人类 aGVHD 发病机制的积极参与者。
