Interleukin-15 enhances the expansion and function of natural killer T cells from adult peripheral and umbilical cord blood.
Invariant natural killer T cells (iNKT cells) are innate-like non-conventional T cells restricted by the CD1d molecule that are unique in their ability to play a pivotal role in immune regulation. Deficient iNKT function has been reported in patients receiving umbilical cord blood (UCB) transplantation. We sought to determine the effect of interleukin (IL)-15 on α-galactosylceramide (α-GalCer)-expanded iNKT cell function from UCB and adult peripheral blood (APB) mononuclear cells (MNCs). Fresh APB and UCB MNCs were cultured with IL-15 (50 ng/ml) in the presence or absence of α-GalCer (100 ng/ml) for 10 days. Cells were harvested for examination of cell yield, apoptosis, cytokine production and cytotoxic function of Vα24(+)/Vβ11(+) iNKT cells. We observed that α-GalCer-expanded APB and UCB iNKT cells and such expansion was further enhanced with IL-15. The percentage of CD3(+)CD56(+) NKT-like cells in both APB and UCB MNCs was increased with IL-15 but not with α-GalCer. Apoptosis of UCB iNKT cells was ameliorated by IL-15. Although APB and UCB iNKT cells secreted lower IFN-γ, it could be enhanced with IL-15. The expression of perforin in APB iNKT cells can also be enhanced with IL-15. UCB Vα24(+)Vβ11(+) iNKT cells further augmented K562 cytotoxicity mediated by IL-15. Taken together, these results demonstrated the relative functional deficiencies of α-GalCer induced UCB iNKT cells, which can be ameliorated by IL-15. Our findings suggest a therapeutic benefit of IL-15 immunotherapy during the post-UCB transplant period when iNKT function remains poor.
Division of Asthma, Allergy, and Rheumatology, Department of Pediatrics, Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Kwei-Shan, Tao-Yuan, Taiwan.
Syh-Jae
SJ
Lin
Department of Neurosurgery, Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Kwei-Shan, Tao-Yuan, Taiwan.
Ying-Cheng
YC
Huang
Department of Obstetrics/Gynecology, Chang Gung Memorial Hospital, 5 Fu-Hsing Street, Kwei-Shan, Tao-Yuan, Taiwan.
Po-Jen
PJ
Cheng
Health Research Division, Chang Gung Children's Hospital, 5 Fu-Hsing Street, Kwei-Shan, Tao-Yuan, Taiwan.
Pei-Tzu
PT
Lee
Health Research Division, Chang Gung Children's Hospital, 5 Fu-Hsing Street, Kwei-Shan, Tao-Yuan, Taiwan.
Hsiu-Shan
HS
Hsiao
Department of Microbiology and Immunology, Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kwei-Shan, Tao-Yuan, Taiwan. Electronic address: mingling@mail.cgu.edu.tw.
Ming-Ling
ML
Kuo
D000328:Adult; D017209:Apoptosis; D049109:Cell Proliferation / Q000502:physiology*; D005312:Fetal Blood / Q000276:immunology*; D006801:Humans; D019409:Interleukin-15 / Q000502:physiology*; D055611:Natural Killer T-Cells / Q000166:cytology / Q000276:immunology*
D019409:Interleukin-15