Killing effects of anti-CD158 monoclonal antibody-modified NK cells against the allogeneic dendritic cells / 中华器官移植杂志

ABSTRACT

Objective To investigate the killing effect of donor NK cells on recipient dentritic cells (DCs) by blocking KIR2DL1 and KIR2DL3 with monoclonal antibodies CD158a and CD158b,and the possible mechanism about donor NK cells reducing the incidence of graft versus host disease (GVHD).Methods SSP-PCR was used to examine the genotypic makeup of KIR in 15 pairs of patients and their HLA-identical sibling hematopoietic stem cell transplantation (HSCT) donors in our department.Peripheral blood mononuclear cells (PBMC) from 15 pairs of patients and their donors were extracted and preserved,and donor NK cells were isolated by DYNABEADS UNTOUCHED HUMAN NK sorting kit.Methyl thiazolyl tetrazolium (MTT) reduction assay was used to detect the killing activity of donor NK cells against recipients DCs.To observe the different NK killing activity before and after KIR receptors blockade,the anti-CD158a and CD158b monoclonal antibodies were used to block KIR inhibitory receptors.Results The killing effect of donor NK cells was significantly enhanced after inhibitory receptor KIRs blockades,the killing effect of NK cells in HVG KIR ligandmismatching pattern group was significantly higher than GVH or KIR receptor-ligand matched pattern group.The killing effect became stronger when the dose of antibody was increased.ConclusionIt is demonstrated in vitro that the killing effect of alloreactive NK cells could be enhanced by KIR functional modification,and the infusion of alloreactive NK cells could be used as a new strategy of immunotherapy for GVHD.