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. This report describes a limiting-dilution assay system which uses low input numbers of HTLV-1-producing cells for generation of T-lymphocyte cultures. The HTLV-1 transformants generated with this assay system produced high levels of HTLV-1 p24 antigen and required exogenous cytokines for maintenance. Clonal populations of CD4- or CD8-positive HTLV-1 transformants were generated with transformation efficiency rates as high 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), such as IL-4 or IL-7. IL-4- or IL-7-dependent HTLV-1 transformants underwent T-lymphocyte mitogenesis in response to their homologous cytokines but proliferated best in the presence of IL-2. Since the receptors for 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.
Persaud
D
D
Department of Pediatrics, New York University Medical Center, New York 10016, USA.
Muñoz
J L
JL
Tarsis
S L
SL
Parks
E S
ES
Parks
W P
WP
D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D002460:Cell Line; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002999:Clone Cells; D046508:Culture Techniques / Q000379:methods; D016207:Cytokines / Q000494:pharmacology*; D005434:Flow Cytometry; D015329:Gene Rearrangement, T-Lymphocyte; D006684:HLA-DR Antigens / Q000032:analysis; D015368:Human T-lymphotropic virus 1 / Q000276:immunology* / Q000472:pathogenicity / Q000502:physiology; D006801:Humans; D016130:Immunophenotyping; D007700:Kinetics; D008213:Lymphocyte Activation; D015203:Reproducibility of Results; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology* / Q000821:virology*; D013997:Time Factors
D016207:Cytokines; D006684:HLA-DR Antigens