Reduced expression of Bcl-2 in CD8⁺ T cells deficient in the IL-15 receptor α-chain

Mice that lack IL-15 or the IL-15R α-chain (IL-15Rα) are deficient in peripheral CD8⁺, but not in CD4⁺, T cells. This CD8⁺ T cell-specific deficiency has now been investigated further by characterization of a new strain of IL-15Rα^-/- mice. The adult mutant mice exhibited a specific reduction in the percentage of CD8-single positive TCR^high thymocytes. The expression of Bcl-2 was reduced in both CD8⁺ thymocytes and naive T cells of the mutant animals, and the susceptibility of these cells to death was increased. Memory CD8⁺ cells were profoundly deficient in IL-15Rα^-/-mice, and the residual memory-like CD8⁺ cells contained a high percentage of dead cells and failed to up-regulate Bcl-2 expression compared with naive CD8⁺ cells. Moreover, exogenous IL-15 both up-regulated the level of Bcl-2 in and reduced the death rate of wild-type and mutant CD8⁺ T cells activated in vitro. These results indicate that IL-15 and IL-15Rα regulate the expression of Bcl-2 in CD8⁺ T cells at all developmental stages. The reduced Bcl-2 content in CD8⁺ cells might result in survival defect and contribute to the reduction of CD8⁺ cells in IL.15Rα^-/-mice.