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

• Published in: The Journal of immunology (1950) Vol. 168; no. 2; pp. 705 - 712
• Main Authors: Wu, Tzong-Shoon, Lee, Jan-Mou, Lai, Yein-Gei, Hsu, Jen-Chi, Tsai, Ching-Yen, Lee, Ying-Hue, Liao, Nan-Shih
• Format: Journal Article
• Language: English
• Published: United States 15.01.2002
• Subjects: Animals; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - pathology; Cell Death - genetics; Cell Death - immunology; Cell Differentiation - genetics; Cell Differentiation - immunology; Crosses, Genetic; Female; Interleukin-15 - genetics; Interleukin-15 - pharmacology; Lymphocyte Subsets - immunology; Lymphocyte Subsets - pathology; Lymphopenia - genetics; Lymphopenia - immunology; Lymphopenia - pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Transgenic; Proto-Oncogene Proteins c-bcl-2 - antagonists & inhibitors; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Receptors, Interleukin-15; Receptors, Interleukin-2 - deficiency; Receptors, Interleukin-2 - genetics; Thymus Gland - immunology; Thymus Gland - pathology; Up-Regulation - genetics; Up-Regulation - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.168.2.705

Mice that lack IL-15 or the IL-15R alpha-chain (IL-15Ralpha) 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-15Ralpha(-/-) 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-15Ralpha(-/-)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-15Ralpha 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-15Ralpha(-/-)mice.