Diseases associated with human T-cell lymphotropic virus-I (HTLV-I) infection are highly variable in their clinical manifestation, suggesting diverse mechanisms of pathogenesis. These studies were undertaken to assess in vitro correlates of disease outcome. A feature of HTLV-I- infected lymphocytes is spontaneous proliferation in culture in the absence of added mitogens or cytokines. We have studied proliferation of lymphocytes in culture with cells obtained from patients with adult T-cell leukemia (ATL), tropic spastic paraparesis (TSP), children with infectious dermatitis, and HTLV-I disease-free individuals. Spontaneous proliferation was measured by 3H-thymidine incorporation and virus production by assay for p24 gag proteins and messenger RNA. Virus expression was low as was spontaneous proliferation in cells of patients with ATL. Cells from individuals with TSP and from children with infectious dermatitis had higher levels of proliferation and virus production. HTLV-I carriers had variable levels of proliferation and virus production. To determine the subpopulation infected, cells bearing lymphocyte subset markers were separated by fluorescence-activated cell sorting, and cells were cultured with and without antibodies to viral proteins and cell surface structures that regulated cell to cell interaction. Antibodies to CD3 and the alpha/beta T-cell receptors (TCRs) increased proliferation and virus production, while antibodies to HLA class I suppressed both virus production and spontaneous lymphocyte proliferation. The immunosuppressive compound, cyclosporin A, shut down cell activation but did not affect virus production. Virus production was localized to the cells bearing the alpha/beta TCRs. HTLV-I-infected CD4+ cells were investigated for the alpha/beta TCR families. Restricted alpha/beta chains were expressed in infected cells. Subpopulations of cells from HTLV-II-infected individuals were separated by flow cytometric techniques and the presence of provirus determined. In nine of ten subjects, virus was found in CD8+ cells and in three of these individuals, virus was also found at low levels in CD4+ cells. In one individual virus infection was found only in the CD4+ subpopulation.
