Promotion of early osteoclastogenesis and B lymphopoiesis in the bone marrow of transgenic rats with the env-pX gene of human T-cell lymphotropic virus type I

Human T-cell lymphotropic virus type I(HTLV-I) is associated with various c linical disorders including adult T cell leukemia, myelopathy, arthropathy. Hypercalcemia resulting from osteoclast activation and a variety of hemato poietic abnormalities have been also observed in HTLV-I infected patients, however, precise mechanism about initial trigger(s) prior to presenting sym ptoms is still unknown. In this study, to assess effects of HTLV-I on hemat opoiesis, we analysed characteristics of early hematopoietic precursors in HTLV-I env-pX transgenic rats. Progenitor cells for osteoclasts were signif icantly increased even in the marrow of asymptomatic env-pX rats. Progenito rs for B cells were also highly enriched, while colony forming cells (CFC) elicited by GM-CSF(CFU-GM) and M-CSF(CFU-M) were comparable to normal litte rmates. Following arthritis in env-pX transgenic rats, osteoclastogenesis w as further augmented and the CFCs were increased. Bone marrow cells carryin g adjuvant-induced arthritis retained a constant number of progenitors for osteoclast and B lymphocytes, whereas the number of CFU-CM and CFU-M increa sed. These results indicate that the env-pX transgene affect early stages o f osteoclast and B-cell lineages prior to developing diseases, in contrast, an increase of the CFCs was caused indirectly by arthritis. This study pro vides a novel standpoint for the mechanisms of pathogenesis by HTLV-I.