ALTERATION OF THE CD34 +Tf-1β 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-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 IL-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 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.