The role of monocytes in the regulation of GVHD after allogeneic stem cell transplantation.

尽管粒细胞集落刺激因子（G-CSF）动员的外周血单核细胞（G-PBMC）移植物含有比标准骨髓移植物多至少10倍的T细胞，但急性移植物抗宿主病（aGVHD）的发生率和严重程度并不高于用同种异体骨髓观察到的。我们已经证明，在CD 4+细胞中共刺激分子CD 28应答复合物的诱导似乎被G-PBMC中CD 14+细胞的存在所抑制。最近的研究表明，NK细胞上的抑制性自然杀伤细胞受体（NKRs）通过与MHC I类分子的结合来负调节NK细胞和T细胞的功能。CD 94/NKG 2异二聚体作为HLA-E非经典HLA-I分子的受体。我们发现，CD 94/NKG 2A在对常规免疫抑制治疗反应良好的cGVHD患者中的表达高于反应差的cGVHD患者。此外，我们还报道了混合淋巴细胞培养（MLC）后G-PBMC中CD 8 + T细胞上CD 94/NKG 2A的表达增加。然而，当使用CD 14去除的G-PBMC时，CD 94/NKG 2A表达没有增加。向去除CD 14的G-PBMC中加入纯化的CD 14+细胞以剂量依赖性方式诱导CD 94/NKG 2A表达，然而，纯化的CD 14+细胞对CD 94/NKG 2A表达的这种增强作用被应答细胞和CD 14+细胞之间存在的膜抑制。因此，G-PBMC中的CD 14+细胞诱导CD 8 + T细胞上的CD 94/NKG 2A表达，这反过来似乎下调同种异体应答。因此，抑制T细胞上的NKR表达在同种异体反应的调节中具有重要作用。

Although granulocyte colony-stimulating factor (G-CSF)-mobillized peripheral blood mononuclear cells (G-PBMC) grafts contain at least ten times more T cells than standard bone marrow grafts, the incidence and severity of acute graft-versus-host disease (aGVHD) is not higher than that observed with allogeneic marrow. We have shown that the induction of constimulatory molecule CD28 responsive complex in CD4+ cells appears to be suppressed by the presence of CD14+ cells in the G-PBMCIt has recently been shown that inhibitory natural killer cell receptors (NKRs) on NK cells negatively regulate NK cell and also T cell functions through their binding to MHC class I molecules. A CD94/NKG2 heterodimer serves as a receptor for HLA-E non-classical HLA-I molecules. We showed the expression of CD94/NKG2A on T cells was higher in cGVHD patients with good response to conventional immunosuppressive therapy than in cGVHD patients with poor response. Also, we reported the increased expression of CD94/NKG2A on CD8+ T cells in G-PBMC after mixed lymphocyte culture (MLC). However, CD94/NKG2A expression did not increase when CD14-depleted G-PBMC was used. The addition of purified CD14+ cells to CD14-depleted G-PBMC induced CD94/NKG2A expression in a dose-dependent fashion, however, this enhancing effect of purified CD14+ cells on CD94/NKG2A expression was inhibited by the presence of a membrane between responder cells and CD14+ cells. Therefor, CD14+ cells in G-PBMC induce CD94/NKG2A expression on CD8+ T cells, which in turn appear to down-regulate alloresponses. Therefore, inhibitory NKR expression on T cells has an important role in the regulation of alloresponse.