ALTERATION OF THE CD34(-1-BETA CELL-LINE PROFILE IN RESPONSE TO LONG-TERM EXPOSURE TO IL-15() TF)

Interleukin 15 IL-15) is a cytokine with many functional characteristi cs 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 co mparison to IL-2. These studies were performed using the growth factor -dependent myelomonocytic cell line, Tf-1, which has been well charact erized with regard to morphology, CD marker expression, responses to c ertain growth factors and cytokines (GM-CSF, IL-4, erythropoietin), an d can differentiate through the myeloid and erythroid lineages. In ord er to study IL-2 and IL-15 responses, Tf-l cells were retrovirally inf ected with the IL-2R beta chain gene as a means to confer IL-2 respons iveness to this cell type. The results of this study demonstrate that retroviral infection of Tf-l successfully generated a stable IL-2 resp onsive cell line, Tf-1 beta, without interfering with the original cha racteristics of the Tf-l 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 mark er expression, esterase activity and proliferative response is unalter ed 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, a nd HLA-DR, and a decreased response to IL-15 in comparison to Tf-1 bet a 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 prof ile. Furthermore, the production of the Tf-1 beta 2 and Tf-1 beta 15 s ublines demonstrates that IL-2 and IL-15 can support long-term cell gr owth. However, this long-term growth in IL-15 leads to subtle alterati ons in the cell profile that are not seen with IL-2, suggesting that d istinctions 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 dist inctions between IL-2 and IL-15. (C) 1997 Academic Press Limited.