[Effects of interleukin 21 on anti-leukemia activity of cytotoxic T lymphocytes induced by dendritic cells].
This study was aimed to explore the effects of interleukin 21 (IL-21) on the anti-leukemia activity of cytotoxic T lymphocytes (CTL) induced by dendritic cells (DCs) in vitro. The peripheral mononuclear cells from leukemia patients in complete remission were cultured with the specific cytokines to induce the production of DCs. The DCs loaded with RNA from autologous leukemic cells as antigen, and co-cultured with autologous T lymphocytes to get leukemia specific CTL. The cytotoxic activity of CTL against autologous leukemic cells was measured by LDH release method. The concentration of IFN-gamma and TNF-alpha in the culture supernatant was measured by enzyme immunoassay. The effects of IL-21 on the mature DCs were also studied by the measurement of the phenotype of DC and the allogenic mixed lymphocytic reactions induced by DCs. Experiments were divided into 2 groups: test group in which IL-21 (200 ng/ml) was added in coculture of DC/CTL and control group in which no IL-21 (200 ng/ml) was added. The results showed that when cultured with IL-21, the quantity of CTL increased from (56.73 +/- 10.21)% (control group) to (73.43 +/- 18.01)% (p < 0.01); The concentration of IFN-gamma and TNF-alpha in the culture supernatant increased from (154.91 +/- 67.20) ng/L (control group) to (310.62 +/- 141.15) ng/L (p < 0.01) and from (8.77 +/- 5.09) microg/L (control group) to (15.25 +/- 6.56) microg/L (p < 0.01) respectively. At the effector: target ratio of 20:1, the cytotoxic activity against autologous leukemic cells by CTL increased from (50.22 +/- 5.07)% (control group) to (75.38 +/- 9.47)% (p < 0.01). IL-21 had neither effect on the phenotype (CD1a, CD83, CD86, CD80 and HLA-DR) of mature DCs nor the allogeneic mixed lymphocytic reactions induced by DCs. It is concluded that IL-21 can strengthen the proliferation of CTL, and improve the production of IFN-gamma and TNF-alpha, thus enhance the anti-leukemia activity of CTL. Nevertheless, there is no effect of IL-21 on the function of mature DCs. These data indicate that IL-21 has a potential clinical value in the enhancement of anti-leukemia immunotherapy.
Zhao
Ming-Feng
MF
Department of Hematology, Tianjin First Central Hospital, Tianjin, China. zmfzmf@hotmail.com
Zhai
Weng-Jing
WJ
Deng
Qi
Q
Li
Yu-Ming
YM
Geng
Li
L
Yang
Li
L
Lv
Hai-Rong
HR
Lin
Xue-Mei
XM
Liu
Peng-Jiang
PJ
Li
Jing-Lan
JL
D000328:Adult; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects*; D049109:Cell Proliferation; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003713:Dendritic Cells / Q000166:cytology / Q000187:drug effects*; D005260:Female; D006801:Humans; D007371:Interferon-gamma / Q000276:immunology; D007378:Interleukins / Q000494:pharmacology*; D020014:K562 Cells; D007938:Leukemia / Q000188:drug therapy / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D055815:Young Adult; D000098546:Interleukin-21
D007378:Interleukins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D000098546:Interleukin-21