IL-15 Promotes the Survival of Naive and Memory Phenotype CD8 super(+) T Cells

• Published in: The Journal of immunology (1950) 2003-05, Vol.170 (10), p.5018-5026
• Main Authors: Berard, M, Brandt, K, Paus, S B, Tough, D F
• Format: Article
• Language: English
• ISSN: 0022-1767

IL-15 stimulates the proliferation of memory phenotype CD44 super(high)CD8 super(+) 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 (CD44 super(low)) CD8 super(+) T cells. We report that IL-15 promotes the survival of both CD44 super(low) and CD44 super(high) CD8 super(+) T cells, doing so at much lower concentrations than required to induce proliferation of CD44 super(high) cells. Rescue from apoptosis was associated with the up-regulation of Bcl-2 in both cell types, whereas elevated expression of Bcl-x sub(L) was observed among CD44 super(high) but not CD44 super(low) CD8 super(+) 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 CD44 super(high)CD8 super(+) cells to express higher levels of IL-15R beta than CD44 super(low) 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 super(+) T cells.