IL-2 and IL-15 exhibit opposing effects on Fas mediated apoptosis.
It has been shown that IL-2 and IL-15 can have opposing effects on life and death of T cells. However, the role of IL-2 and IL-15 in regulating the fate of other cell types is less clear. In the present study, we examined the impact of IL-2 and IL-15 on life and death of pre-B cells using the BAF-B03 line. We showed that BAF-B03 cells constitutively expressed the private IL-2R alpha chain and IL-15R alpha chain, and the shared IL-2R beta chain and gamma c chain. Stimulation of BAF-B03 cells in vitro with IL-2 and IL-15 induced vigorous cell proliferation in a dose-dependent fashion. Titration of IL-2 and IL-15 in the assay showed that the mitotic effects of IL-2 and IL-15 were remarkably similar. However, the sensitivities of BAF-B03 cells to Fas mediated apoptosis after IL-2 and IL-15 stimulation were strikingly different. Cells cultured in IL-2 readily underwent apoptotic cell death upon cross-linking of the Fas receptor whereas cells cultured in IL-15 were extremely resistant to Fas triggered cell death. The anti-apoptotic effect of IL-15 in this model was associated with increased expression of Bcl-xL. FLIP expression, however, was comparable between IL-2 and IL-15 stimulated cells. We conclude that IL-2 and IL-15 have diametrically opposite effect on the fate of BAF-B03 cells, although both cytokines share similar receptor structure and exhibit similar mitotic activities.
Demirci
Gulcin
G
Department of Medicine, Harvard Medical School, Division of Immunology, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA.
Li
Xian Chang
XC
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D002460:Cell Line; D006801:Humans; D019409:Interleukin-15 / Q000378:metabolism*; D007376:Interleukin-2 / Q000378:metabolism*; D051379:Mice; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2 / Q000378:metabolism; D051025:bcl-Associated Death Protein / Q000378:metabolism; D051020:bcl-X Protein / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism*
C508024:IL15RA protein, human; C508025:Il15ra protein, mouse; D019409:Interleukin-15; D007376:Interleukin-2; D053647:Receptors, Interleukin-15; D015375:Receptors, Interleukin-2; D051025:bcl-Associated Death Protein; D051020:bcl-X Protein; D019014:fas Receptor