Alteration of the CD34+ Tf-1β cell line profile in response to long-term exposure to IL-15

Nancy L. Farner, Jacek Gan, Jill L O De Jong, Thomas P. Leary, Timothy S. Fenske, Patrick Buckley, Sabrina Dunlap, Paul M. Sondel

Research output: Contribution to journalArticle

13 Scopus citations

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-2Rβ 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 1L-2 responsive cell line, Tf-1β, without interfering with the original characteristics of the Tf-1 cell. Tf-1β cells respond functionally to both IL-2 and IL-15. When Tf-1β cells are grown for 8 weeks in IL-2 (Tf-1β2), 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-1β line maintained in GM-CSF. However, long-term growth of Tf-1β in IL-15 (Tf-1β15) results in morphological alterations, downregulation of CD33, CD38, and HLA-DR, and a decreased response to IL-15 in comparison to Tf-1β2. 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-1β2 and Tf-1β15 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-1β15 cell line will be useful to clarify these functional distinctions between IL-2 and IL-15.

Original languageEnglish (US)
Pages (from-to)316-327
Number of pages12
JournalCytokine
Volume9
Issue number5
DOIs
StatePublished - May 1997

Keywords

  • CD34
  • IL-15
  • Retrovirus
  • TF-1β cell line

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Biochemistry
  • Hematology
  • Molecular Biology

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    Farner, N. L., Gan, J., De Jong, J. L. O., Leary, T. P., Fenske, T. S., Buckley, P., Dunlap, S., & Sondel, P. M. (1997). Alteration of the CD34+ Tf-1β cell line profile in response to long-term exposure to IL-15. Cytokine, 9(5), 316-327. https://doi.org/10.1006/cyto.1996.0171