Possible involvement of allogeneic antigens recognised by donor-derived CD4 cytotoxic T cells in selective GVL effects after stem cell transplantation of patients with haematological malignancy.
Cytotoxic T lymphocyte (CTL) lines specific for allogeneic antigens were generated by in vitro stimulation of donor-derived peripheral blood mononuclear cells obtained from patients who received human leucocyte antigen (HLA)-matched allogeneic haematopoietic stem cell transplantation (HSCT). One of the allogeneic antigen-specific CD4+ CTL lines, CTL-A, generated from a patient with T cell acute lymphoblastic leukaemia, recognised HLA-DPB1*0501-positive Epstein-Barr virus-immortalised human B cell line (EBV-B cells), phytohaemagglutinin blasts and leukaemia cells, but not interferon-gamma (IFN-gamma) treated HLA-DPB1*0501-positive fibroblasts, indicating that this CD4+ T-cell line recognised a minor histocompatibility antigen (mHa) that is preferentially expressed in haematopoietic cells in an HLA-DPB1*0501-restricted manner. The other CD4+ CTL line, CTL-B, generated from a patient with chronic myeloid leukaemia, recognised mismatched HLA-DQB1*0303 on EBV-B cells and phytohaemagglutinin (PHA) blasts. Interestingly, this CTL line did not recognise IFN-gamma-treated recipient's skin fibroblasts, as HLA-DQ was merely upregulated even after IFN-gamma stimulation in non-haematopoietic cells including fibroblasts, endothelial cells and hepatocytes. These results suggest that these CD4 positive CTLs, specific for mismatch HLA-DQ and mHa that are preferentially expressed on haematopoietic cells, may play an important role in induction of selective graft-versus-leukaemia effect without development of graft-versus-host disease after allogeneic HSCT.
Matsushita
Maiko
M
Division of Cellular Signaling, Institute for Advanced Medical Research, Keio University School of Medicine, Tokyo, Japan.
Yamazaki
Rie
R
Ikeda
Hideyuki
H
Mori
Takehiko
T
Sumimoto
Hidetoshi
H
Fujita
Tomonobu
T
Okamoto
Shinichiro
S
Ikeda
Yasuo
Y
Kawakami
Yutaka
Y
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D005260:Female; D005802:Genes, MHC Class II; D006086:Graft vs Host Disease / Q000517:prevention & control; D020544:Graft vs Leukemia Effect / Q000276:immunology*; D006682:HLA-DP Antigens / Q000032:analysis; D006683:HLA-DQ Antigens / Q000032:analysis; D019337:Hematologic Neoplasms / Q000276:immunology / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human; D006650:Histocompatibility Testing; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007938:Leukemia / Q000276:immunology; D008297:Male; D014407:Tumor Cells, Cultured
D018984:Epitopes, T-Lymphocyte; D006682:HLA-DP Antigens; D006683:HLA-DQ Antigens; D007371:Interferon-gamma