TIME-COURSE AND CYTOKINE DEPENDENCE OF HUMAN T-CELL LYMPHOTROPIC VIRUS TYPE-1 T-LYMPHOCYTE TRANSFORMATION AS REVEALED BY A MICROTITER INFECTIVITY ASSAY

Human T-cell lymphotropic virus type 1 (HTLV-1) enhances the growth of T lymphocytes, allowing the generation of T-lymphocyte cell lines. Th is report describes a limiting-dilution assay system which uses low in put numbers of HTLV-1-producing cells for generation of T-lymphocyte c ultures. The HTLV-1 transformants generated with this assay system pro duced high levels of HTLV-1 p24 antigen and required exogenous cytokin es for maintenance. Clonal populations of CD4- or CD8-positive HTLV-1 transformants were generated with transformation efficiency rates as h igh as 78%. An exogenous cytokine is necessary for HTLV-1 T-lymphocyte transformation, and cytokine dependence is the most likely outcome of infection and transformation. HTLV-1 T-lymphocyte transformation can occur in the presence of cytokines other than interleukin-2 (IL-2), su ch as IL-4 or IL-7. IL-4- or IL-7-dependent HTLV-1 transformants under went T-lymphocyte mitogenesis in response to their homologous cytokine s but proliferated best in the presence of IL-2. Since the receptors f or IL-2, IL-4, and IL-7 share the IL-2 gamma chain, this component may be the common element in the signaling pathway for HTLV-1-associated transformation.