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The Journal of Immunology, 2003, 170: 5018-5026.
Copyright © 2003 by The American Association of Immunologists

IL-15 Promotes the Survival of Naive and Memory Phenotype CD8+ T Cells1

Marion Berard*, Katja Brandt{dagger}, Silvia Bulfone Paus{dagger} and David F. Tough2,*

* Edward Jenner Institute for Vaccine Research, Compton, Newbury, Berkshire, United Kingdom; and {dagger} Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany

IL-15 stimulates the proliferation of memory phenotype CD44highCD8+ T cells and is thought to play a key role in regulating the turnover of these cells in vivo. We have investigated whether IL-15 also has the capacity to affect the life span of naive phenotype (CD44low) CD8+ T cells. We report that IL-15 promotes the survival of both CD44low and CD44high CD8+ T cells, doing so at much lower concentrations than required to induce proliferation of CD44high cells. Rescue from apoptosis was associated with the up-regulation of Bcl-2 in both cell types, whereas elevated expression of Bcl-xL was observed among CD44high but not CD44low CD8+ cells. An investigation into the role of IL-15R subunits in mediating the effects of IL-15 revealed distinct contributions of the {alpha}- and {beta}- and {gamma}-chains. Most strikingly, IL-15R{alpha} was not essential for either induction of proliferation or promotion of survival by IL-15, but did greatly enhance the sensitivity of cells to low concentrations of IL-15. By contrast, the {beta}- and {gamma}-chains of the IL-15R were absolutely required for the proliferative and pro-survival effects of IL-15, although it was not necessary for CD44highCD8+ cells to express higher levels of IL-15R{beta} than CD44low cells to proliferate in response to IL-15. These results show that IL-15 has multiple effects on CD8 T cells and possesses the potential to regulate the life span of naive as well as memory CD8+ T cells.


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