A vigorous production of human T lymphotropic virus type I (HTLV-I)-infected CD4+ T cells is closely associated with the development of adult T cell leukemia (ATL) and neurological disease. However, the immunological mechanisms leading to generation of the HTLV-I-infected cells are not fully clarified. The modulation of CD80 and CD86 expression on the HTLV-I-infected cells and its physiological role in the interaction of infected CD4+ T cells with uninfected CD4+ T cells was examined. The HTLV-I-infected CD4+ T cell lines established from ATL patients and normal donors by infecting their CD4+ T cells with the virus expressed CD80, CD86, and HLA-DR, and induced a proliferation of autologous and allogenic CD4+ T cells. While the CD4+ T cells stimulated with the autologous HTLV-I-infected cells for 7 days expressed CD80 and CD86 but not HTLV-I gene products, they expressed HTLV-I gag antigen after 4 weeks. The interaction of HTLV-I-infected and -uninfected CD4+ T cells was profoundly suppressed by a combination of CD80 and CD86 monoclonal antibodies. These results suggest that the induction of CD80 and CD86 on HTLV-I-infected CD4+ T cells participates actively in the generation of the virus-infected progenitor cells.