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.