Herpesvirus saimiri immortalized gamma delta T cell line activated by IL-12.
IL-12 is a novel heterodimeric cytokine important for the regulation and differentiation of lymphocytes and NK cells. Like other cytokines, IL-12 mediates its biologic activity through high-affinity receptors expressed on responsive cells. To date, a large number of receptors for IL-12 have been found only on PBMC following activation with PHA or IL-2. To gain further knowledge of the IL-12R complex and the IL-12 signal transduction pathway in cytotoxic T cells, we studied a number of human T cell lines that had been transformed to permanent growth with Herpesvirus saimiri, an oncogenic virus of nonhuman primates. This paper reports the expression of IL-12R on a human gamma delta T cell line that responds to IL-12 with enhanced cytolytic activity and increased expression of cytolytic effector molecules granzyme B and perforin. Using these T cells as a model of IL-12 signal transduction, we confirmed that these events involve members of the Janus kinase family of nonreceptor tyrosine kinases JAK2, TYK2, and signal transducer and activator of transcription 4.
Klein
J L
JL
Division of Hematology and Oncology, Barbara Ann Karmanos Cancer Institute, Wayne State University, Detroit, MI 48201, USA.
Fickenscher
H
H
Holliday
J E
JE
Biesinger
B
B
Fleckenstein
B
B
D002461:Cell Line, Transformed; D002472:Cell Transformation, Viral; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000378:metabolism; D006567:Herpesvirus 2, Saimiriine / Q000502:physiology*; D006801:Humans; D018664:Interleukin-12 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D008213:Lymphocyte Activation / Q000187:drug effects*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D011506:Proteins / Q000378:metabolism; D011518:Proto-Oncogene Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D050797:STAT4 Transcription Factor; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology* / Q000821:virology; D053634:TYK2 Kinase; D015534:Trans-Activators / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D004268:DNA-Binding Proteins; D007376:Interleukin-2; D011506:Proteins; D011518:Proto-Oncogene Proteins; D016692:Receptors, Antigen, T-Cell, gamma-delta; D050797:STAT4 Transcription Factor; C494090:STAT4 protein, human; D015534:Trans-Activators; D018664:Interleukin-12; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507933:JAK3 protein, human; D053614:Janus Kinase 2; D053616:Janus Kinase 3; D053634:TYK2 Kinase; C070139:TYK2 protein, human