title: Alteration of the CD34+ Tf-1 beta cell line profile in response to long-term exposure to IL-15.
abstract: Interleukin 15 (IL-15) is a cytokine with many functional characteristics that are similar to IL-2. Most of the functional activities that IL-2 and IL-15 support have been evaluated in short-term assays. It was our intention, then, to determine the long-term effects of IL-15 in comparison to IL-2. These studies were performed using the growth factor-dependent myelomonocytic cell line, Tf-1, which has been well characterized with regard to morphology, CD marker expression, responses to certain growth factors and cytokines (GM-CSF, IL-4, erythropoietin), and can differentiate through the myeloid and erythroid lineages. In order to study IL-2 and IL-15 responses, Tf-1 cells were retrovirally infected with the IL-2R beta chain gene as a means to confer IL-2 responsiveness to this cell type. The results of this study demonstrate that retroviral infection of Tf-1 successfully generated a stable IL-2 responsive cell line, Tf-1 beta, without interfering with the original characteristics of the Tf-1 cell. Tf-1 beta cells respond functionally to both IL-2 and IL-15. When Tf-1 beta cells are grown for 8 weeks in IL-2 (Tf-1 beta 2), rather than GM-CSF, the original morphology, CD marker expression, esterase activity and proliferative response is unaltered in comparison to that of the original Tf-1 beta line maintained in GM-CSF. However, long-term growth of Tf-1 beta in IL-15 (Tf-1 beta 15) results in morphological alterations, downregulation of CD33, CD38, and HLA-DR, and a decreased response to IL-15 in comparison to Tf-1 beta 2. These studies support the concept that retroviral infection, even when it confers new functions upon a cell, does not necessarily alter all other functions, as assessed by evaluation of its phenotypic profile. Furthermore, the production of the Tf-1 beta 2 and Tf-1 beta 15 sublines demonstrates that IL-2 and IL-15 can support long-term cell growth. However, this long-term growth in IL-15 leads to subtle alterations in the cell profile that are not seen with IL-2, suggesting that distinctions in IL-2 and IL-15 function do exist. Further study of the Tf-1 beta 15 cell line will be useful to clarify these functional distinctions between IL-2 and IL-15.
authors.affiliation: Department of Human Oncology, University of Wisconsin, Madison, USA.
authors.forename: N L
authors.initials: NL
authors.lastname: Farner
authors.forename: J
authors.initials: J
authors.lastname: Gan
authors.forename: J L
authors.initials: JL
authors.lastname: de Jong
authors.forename: T P
authors.initials: TP
authors.lastname: Leary
authors.forename: T S
authors.initials: TS
authors.lastname: Fenske
authors.forename: P
authors.initials: P
authors.lastname: Buckley
authors.forename: S
authors.initials: S
authors.lastname: Dunlap
authors.forename: P M
authors.initials: PM
authors.lastname: Sondel
mesh_terms: D036541:ADP-ribosyl Cyclase; D051997:ADP-ribosyl Cyclase 1; D015703:Antigens, CD / Q000096:biosynthesis; D018952:Antigens, CD34 / Q000276:immunology*; D000943:Antigens, Differentiation / Q000096:biosynthesis; D015214:Antigens, Differentiation, Myelomonocytic / Q000096:biosynthesis; D004950:Esterases / Q000378:metabolism; D015870:Gene Expression; D005822:Genetic Vectors; D006684:HLA-DR Antigens / Q000096:biosynthesis; D006801:Humans; D019409:Interleukin-15 / Q000494:pharmacology*; D007376:Interleukin-2 / Q000494:pharmacology*; D008562:Membrane Glycoproteins; D009699:N-Glycosyl Hydrolases / Q000096:biosynthesis; D015375:Receptors, Interleukin-2 / Q000096:biosynthesis / Q000235:genetics; D012190:Retroviridae; D063268:Sialic Acid Binding Ig-like Lectin 3; D013997:Time Factors; D014407:Tumor Cells, Cultured
chemical_list: D015703:Antigens, CD; D018952:Antigens, CD34; D000943:Antigens, Differentiation; D015214:Antigens, Differentiation, Myelomonocytic; C571163:CD33 protein, human; D006684:HLA-DR Antigens; D019409:Interleukin-15; D007376:Interleukin-2; D008562:Membrane Glycoproteins; D015375:Receptors, Interleukin-2; D063268:Sialic Acid Binding Ig-like Lectin 3; D004950:Esterases; D009699:N-Glycosyl Hydrolases; D036541:ADP-ribosyl Cyclase; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1