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

Cytokine. 1997 May;9(5):316-27. doi: 10.1006/cyto.1996.0171.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • ADP-ribosyl Cyclase
  • ADP-ribosyl Cyclase 1
  • Antigens, CD / biosynthesis
  • Antigens, CD34 / immunology*
  • Antigens, Differentiation / biosynthesis
  • Antigens, Differentiation, Myelomonocytic / biosynthesis
  • Esterases / metabolism
  • Gene Expression
  • Genetic Vectors
  • HLA-DR Antigens / biosynthesis
  • Humans
  • Interleukin-15 / pharmacology*
  • Interleukin-2 / pharmacology*
  • Membrane Glycoproteins
  • N-Glycosyl Hydrolases / biosynthesis
  • Receptors, Interleukin-2 / biosynthesis
  • Receptors, Interleukin-2 / genetics
  • Retroviridae
  • Sialic Acid Binding Ig-like Lectin 3
  • Time Factors
  • Tumor Cells, Cultured

Substances

  • Antigens, CD
  • Antigens, CD34
  • Antigens, Differentiation
  • Antigens, Differentiation, Myelomonocytic
  • CD33 protein, human
  • HLA-DR Antigens
  • Interleukin-15
  • Interleukin-2
  • Membrane Glycoproteins
  • Receptors, Interleukin-2
  • Sialic Acid Binding Ig-like Lectin 3
  • Esterases
  • N-Glycosyl Hydrolases
  • ADP-ribosyl Cyclase
  • CD38 protein, human
  • ADP-ribosyl Cyclase 1