ESTABLISHMENT OF A CD4(-CELL CLONE RECOGNIZING AUTOLOGOUS HEMATOPOIETIC PROGENITOR CELLS FROM A PATIENT WITH IMMUNE-MEDIATED APLASTIC-ANEMIA() T)

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 mi tigated by CyA. We established a total of 29 T cell clones from the bo ne marrow of a CyA-dependent AA patient in relapse. Some of the CD4(+) T eel clones demonstrated a specific proliferative response to irradi ated 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 c arried the T cell receptor V beta 17 and produced interferon-gamma (IF N-gamma) only when cultured with autologous CD34(+)-rich cells. This T cell clone inhibited colony formation by colony-forming unit-granuloc yte/macrophage (CFU-GM) and burst-forming unit-erythroid (BFU-E) by ap proximately 60% when it was cultured with autologous CD34(+)-rich tell s in methylcellulose medium, although the clone did not exhibit direct cytotoxicity to the CD34(+)-rich cells. The inhibition of in vitro he matopoietic progenitor cell growth by the T cell clone was partially a brogated by the addition of CyA to the culture. These findings suggest that in some patients with CyA-dependent AA, CD4(+) T cells autoreact ive to hematopoietic progenitor cells exist and may play an important role in the pathogenesis of bone marrow failure.