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

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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.