Bcl-xL is associated with the anti-apoptotic effect of IL-15 on the survival of CD56(dim) natural killer cells.
Human NK cells can be distinguished into CD56(bright) and CD56(dim) subsets based on cell surface CD56 density. It has been shown that IL-2 and IL-15 have opposing effects on life and death of CD8(+) T cells. However, the roles of IL-2 and IL-15 in regulating these two NK cell subsets remain elusive. In this study, we comparatively analyzed the effects of IL-2 and IL-15 on two NK cell subsets. IL-15 improved the proliferation and activation of CD56(dim) NK cells in long-term cord blood mononuclear cell culture, but IL-2 only maintained the survival of CD56(bright) NK cells. The percentage of CD56(+)Annexin V(+) NK cells cultured with IL-15 was lower than that with IL-2; moreover, most of Annexin V(+) NK cells were primarily in the CD56(dim) NK cells. IL-15 cultured NK cells expressed higher level of Bcl-xL than IL-2 cultured cells. Furthermore, IL-15 more strongly upregulated CD25 expression and better maintained the expression of IL-15Ralpha than IL-2. These results suggest that CD56(dim) NK cells undergo apoptosis when cultured with IL-2, but IL-15 inhibits their apoptosis and Bcl-xL is associated with the anti-apoptotic effect of IL-15. So IL-15 played a crucial role in sustaining long-lasting functions of CD56(dim) NK cells.
Zheng
Xiaodong
X
Institute of Immunology, Hefei National Laboratory for Physical Sciences at Microscale, University of Science and Technology of China, Hefei, Anhui 230027, China.
Wang
Yanyan
Y
Wei
Haiming
H
Ling
Bin
B
Sun
Rui
R
Tian
Zhigang
Z
D017209:Apoptosis; D019002:CD56 Antigen / Q000032:analysis; D002470:Cell Survival; D002478:Cells, Cultured; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D019409:Interleukin-15 / Q000276:immunology / Q000378:metabolism*; D007376:Interleukin-2 / Q000276:immunology / Q000378:metabolism*; D007694:Killer Cells, Natural / Q000166:cytology / Q000276:immunology / Q000502:physiology*; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000502:physiology; D051020:bcl-X Protein / Q000378:metabolism*
C494811:BCL2L1 protein, human; D019002:CD56 Antigen; D019409:Interleukin-15; D007376:Interleukin-2; D051020:bcl-X Protein