HUMAN IMMATURE THYMOCYTES AS TARGET-CELLS OF THE LEUKEMOGENIC ACTIVITY OF HUMAN T-CELL LEUKEMIA-VIRUS TYPE-I

The risk of developing adult T-cell leukemia (ATL) associated with neo natal infection by human T-cell leukemia virus type I (HTLV-I) suggest s that early events triggered by HTLV-I might be of crucial importance in initiating the multistep lymphoproliferative process leading sever al decades later to the development of leukemic disease. Thus, infecti on of thymocytes early in life might be directly correlated with the d evelopment of ATL. In the present study, we show that in vitro infecti on of mature (CD2(+)CD3(+)) or immature (CD2(+)CD3(-)) thymocytes resu lted in the exogenous interleukin (IL)-2-dependent proliferation of HT LV-I-positive thymocytes, most of them displaying a CD2(+)CD3(-)CD4(+) phenotype and expressing the CD25 molecule, the cu chain of the IL-2 receptor. Furthermore, the CD80 and CD54 antigens, normally expressed by thymic stromal cells, were detected on these transformed thymocytes , indicating that HTLV-I infection may disturb the cooperation between thymocytes and their thymic environment. These HTLV-I-positive thymoc ytes were producing significant amounts of IL-6, which was found to be implicated in their proliferation and in the expression of CD25, as d emonstrated by blocking experiments using a monoclonal antibody to IL- 6. The present study suggests that immature thymocytes may provide an environment favorable to the unfolding of events reading to leukemia. (C) 1995 by The American Society of Hematology.