Establishment of a CD4+ T cell clone recognizing autologous hematopoietic progenitor cells from a patient with immune-mediated aplastic anemia.
In some patients with aplastic anemia (AA), hematopoietic function is dependent on continuous administration of cyclosporine A (CyA). These AA patients may have T lymphocytes whose myelosuppressive effect is mitigated by CyA. We established a total of 29 T cell clones from the bone marrow of a CyA-dependent AA patient in relapse. Some of the CD4+ T cell clones demonstrated a specific proliferative response to irradiated autologous bone marrow cells enriched for CD34+ cells (CD34(+)-rich cells) obtained from the patient in remission. One of the T cell clones showing the best proliferative response to CD34(+)-rich cells carried the T cell receptor V beta 17 and produced interferon-gamma (IFN-gamma) only when cultured with autologous CD34(+)-rich cells. This T cell clone inhibited colony formation by colony-forming unit-granulocyte/macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) by approximately 60% when it was cultured with autologous CD34(+)-rich cells in methylcellulose medium, although the clone did not exhibit direct cytotoxicity to the CD34(+)-rich cells. The inhibition of in vitro hematopoietic progenitor cell growth by the T cell clone was partially abrogated by the addition of CyA to the culture. These findings suggest that in some patients with CyA-dependent AA, CD4+ T cells autoreactive to hematopoietic progenitor cells exist and may play an important role in the pathogenesis of bone marrow failure.
Nakao
S
S
Third Department of Medicine, Kanazawa University School of Medicine, Ishikawa, Japan.
Takamatsu
H
H
Yachie
A
A
Itoh
T
T
Yamaguchi
M
M
Ueda
M
M
Shiobara
S
S
Matsuda
T
T
D000328:Adult; D000741:Anemia, Aplastic / Q000276:immunology* / Q000473:pathology; D001327:Autoimmune Diseases / Q000276:immunology* / Q000473:pathology; D001853:Bone Marrow / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D002999:Clone Cells / Q000276:immunology; D016572:Cyclosporine / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis; D008297:Male; D011948:Receptors, Antigen, T-Cell / Q000096:biosynthesis
D011948:Receptors, Antigen, T-Cell; D007371:Interferon-gamma; D016572:Cyclosporine