TY - JOUR
T1 - Alteration of the CD34+ Tf-1β cell line profile in response to long-term exposure to IL-15
AU - Farner, Nancy L.
AU - Gan, Jacek
AU - De Jong, Jill L O
AU - Leary, Thomas P.
AU - Fenske, Timothy S.
AU - Buckley, Patrick
AU - Dunlap, Sabrina
AU - Sondel, Paul M.
N1 - Funding Information:
to Dr S[ Wu\ Sally Drew\ M[ T[\ and Linda Sebree\ H[ T[\ "UW!Madison\ Madison\ WI# for technical assistance in generating the morphological data\ and Ms Kristin Elmer "UW!Madison\ Madison\ WI# for ~ow cytometric analysis[ Supported by American Cancer Society Grant No[ IM!567 and National Institutes of Health Grants No[ CA!21574\ p29!CA03419!1\ CM!76189\ and RR92075[ T[ P[ L[ was a Fellow of the American Cancer Society[
PY - 1997/5
Y1 - 1997/5
N2 - 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.
AB - 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.
KW - CD34
KW - IL-15
KW - Retrovirus
KW - TF-1β cell line
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UR - http://www.scopus.com/inward/citedby.url?scp=0031149291&partnerID=8YFLogxK
U2 - 10.1006/cyto.1996.0171
DO - 10.1006/cyto.1996.0171
M3 - Article
C2 - 9195130
AN - SCOPUS:0031149291
SN - 1043-4666
VL - 9
SP - 316
EP - 327
JO - Cytokine
JF - Cytokine
IS - 5
ER -