Isolation of a T-cell clone showing HLA-DRB1*0405-restricted cytotoxicity for hematopoietic cells in a patient with aplastic anemia.
The existence of T cells capable of inhibiting in vitro hematopoiesis has been shown in aplastic anemia (AA), although whether such inhibition is mediated by a specific immune reaction involving an HLA allele remained unknown. We isolated a CD4+ Vbeta21+ T-cell clone that was most dominant among Vbeta21+ T cells in the bone marrow (BM) of an AA patient whose HLA-DRB1 alleles included 1501 and 0405. The T-cell clone named NT4.2 lysed an autologous Epstein-Barr virus-transformed lymphoblastoid cell line (LCL) and phytohemagglutinin-stimulated lymphocytes (PHA-blasts) as well as allogeneic LCLs sharing HLA-DRB1*0405. Cytotoxicity against LCL cells and PHA-blasts by NT4.2 was blocked by anti-HLA-DR monoclonal antibody (MoAb) or anti-CD3 MoAb. NT4.2 also lysed autologous BM mononuclear cells enriched with CD34+ cells that had been cultured for one week in the presence of colony-stimulating factors as well as allogeneic CD34+ cells of a normal individual carrying HLA-DRB1*0405, cultured in the same way. Moreover, NT4.2 strongly inhibited colony formation by hematopoietic progenitor cells derived from cultured CD34+ cells sharing HLA-DRB1*0405. These results indicate that the AA patient has T cells capable of killing hematopoietic cells in an HLA-DRB1*0405-restricted manner and that such cytotoxic T cells may contribute to the pathogenesis of AA.
Nakao
S
S
Third Department of Medicine, Kanazawa University School of Medicine, Ishikawa, Japan.
Takami
A
A
Takamatsu
H
H
Zeng
W
W
Sugimori
N
N
Yamazaki
H
H
Miura
Y
Y
Ueda
M
M
Shiobara
S
S
Yoshioka
T
T
Kaneshige
T
T
Yasukawa
M
M
Matsuda
T
T
D000368:Aged; D000741:Anemia, Aplastic / Q000276:immunology* / Q000473:pathology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D001853:Bone Marrow / Q000276:immunology / Q000469:parasitology / Q000473:pathology; D003114:Colony-Forming Units Assay; D003602:Cytotoxicity, Immunologic; D018076:DNA, Complementary / Q000235:genetics; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006684:HLA-DR Antigens / Q000235:genetics / Q000276:immunology*; D059811:HLA-DRB1 Chains; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D016133:Polymerase Chain Reaction; D018807:Polymorphism, Single-Stranded Conformational; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*
D018076:DNA, Complementary; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D010835:Phytohemagglutinins