Improved detection of clinically significant host-reactive antigens prior to HLA-identical sibling peripheral blood stem cell transplantation using a dendritic cell-based helper T-lymphocyte precursor assay

• Published in: Bone marrow transplantation (Basingstoke) Vol. 33; no. 4; pp. 367 - 375
• Main Authors: SCHWARER, A. P, HEALEY, G, HAMMETT, M
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 01-02-2004
• Subjects: Adult; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy; Animals; Antigens; Assaying; Biological and medical sciences; Blood; Bone marrow, stem cells transplantation. Graft versus host reaction; Cell Line; Cells, Cultured; Clinical significance; Dendritic cells; Dendritic Cells - immunology; Female; Graft versus host disease; Graft vs Host Disease - immunology; Graft-versus-host reaction; Hematopoietic stem cells; Histocompatibility antigen HLA; Histocompatibility Testing - methods; Humans; Incidence; Isoantigens - analysis; Leukocytes (mononuclear); Lymphocyte Culture Test, Mixed - methods; Lymphocyte Culture Test, Mixed - standards; Lymphocytes; Lymphocytes T; Male; Medical sciences; Mice; Middle Aged; Monocytes; Morbidity; Peripheral blood mononuclear cells; Peripheral Blood Stem Cell Transplantation - methods; Peripheral Blood Stem Cell Transplantation - standards; Precursors; Predictive Value of Tests; Siblings; Stem cell transplantation; Stem cells; Stimulators; T-Lymphocytes, Helper-Inducer - immunology; Transfusions. Complications. Transfusion reactions. Cell and gene therapy; Transplantation; Transplantation, Homologous; Transplantation, Isogeneic; Treatment Outcome; Immunopathology; Dendritic cell; Hematology; Stem cell; Precursor cell; Hematopoietic cell; Homograft; Helper cell; Graft versus host reaction; GVHD; Sibling; Precursor; Blood; Antigen; Assay; dendritic cells; Antigen presenting cell; T-Lymphocyte; Bone marrow; Graft; allogeneic BMT; Histocompatibility; HTLp assay
• ISSN: 0268-3369; 1476-5365
• DOI: 10.1038/sj.bmt.1704373

Graft-versus-host disease (GVHD) due to host-reactive antigenic differences between HLA-identical pairs remains an important cause of morbidity and mortality after allogeneic transplantation. The helper T-lymphocyte precursor (HTLp) assay, using peripheral blood mononuclear cells (PBMCs), has been variably shown to detect such host-reactive differences. We assessed whether using dendritic cells (DCs) as the stimulator cells would improve the ability of the HTLp assay to detect these differences. We used PBMCs (standard HTLp assay) or monocyte-derived DCs (DC-HTLp assay) as the stimulator cells for 12 HLA-identical sibling pairs undergoing allogeneic peripheral blood stem cell transplantation. HTLp frequencies were greater by the DC-HTLp assay (median 1:77 712 vs 1:727 514; P=0.008). The standard HTLp assay did not predict for acute GVHD (P=0.42), whereas a trend was noted for the DC-HTLp assay (P=0.095). Of note, of seven patients developing moderately severe to severe acute GVHD, four had a significantly greater DC-HTLp frequency compared to the standard HTLp frequency, whereas all four patients who developed no to moderate acute GVHD had similar HTLp frequencies whether PBMCs or DCs were used as the stimulator cells. Although the small number of donor/recipient pairs assessed limits the strength of any conclusions, our study suggests that the DC-HTLp assay is better able to detect clinically significant host-reactive antigenic differences between HLA-identical siblings.