Correlation of class II transactivator with HLA-DR antigen and its implications.
- Author:
Kai-Lin XU
1
;
Hui LI
;
Xiu-Ying PAN
;
Zhen-Yu LI
;
Qun-Xian LU
;
Ying ZHANG
;
Hong-Hu ZHU
;
Bing DU
;
Ling-Yu ZENG
Author Information
1. Department of Hematology, Affiliated Hospital of Xuzhou Medical College, Xuzhou 221002, China. xukailin@hotmail.com
- Publication Type:Journal Article
- MeSH:
Cells, Cultured;
HLA-DR Antigens;
biosynthesis;
genetics;
Humans;
Interferon-gamma;
pharmacology;
Nuclear Proteins;
biosynthesis;
genetics;
Oligonucleotides, Antisense;
antagonists & inhibitors;
RNA, Messenger;
biosynthesis;
genetics;
STAT1 Transcription Factor;
antagonists & inhibitors;
T-Lymphocytes;
cytology;
Trans-Activators;
biosynthesis;
genetics;
Transplantation Immunology;
immunology
- From:
Journal of Experimental Hematology
2007;15(1):147-151
- CountryChina
- Language:English
-
Abstract:
The present study was purposed to investigate the relation and difference of expression phase between class II transactivator (CIITA) and HLA-DR antigens after IFN-gamma induction, and the inhibition of CIITA and HLA-DR by STAT1-alpha antisense oligonucleotides (STAT1-alpha AS); and to explore the potential effect and significance of CIITA and STAT1-alpha AS in transplantation immunity. T lymphocytes from peripheral blood of healthy subjects were incubated with IFN-gamma at different doses. RT-PCR was used to detect CIITA mRNA and Western blot was used to analyze HLA-DR antigen. Then the optimum dose of IFN-gamma was chosen for the experiment. CIITA mRNA and HLA-DR antigen were detected at various time points. Different doses of STAT1-alpha AS and sense oligonucleotides (STAT1-alpha S) were added to T lymphocytes followed by IFN-gamma. After incubation with IFN-gamma, the expression of CIITA mRNA and HLA-DR was detected once again. The results showed that CIITA mRNA was detectable at 5 hours after IFN-gamma incubation and reached the peak at 14 hours, then declined, but the CIITA mRNA was still found at 23 hours. HLA-DR antigen was detectable at 28 hours after IFN-gamma incubation and reached a peak at 52 hours, then declined. CIITA mRNA expression was positively correlated to HLA-DR expression, and was earlier than the latter. The expression of CIITA mRNA in the AS groups was significantly lower than that in the control group after 5 micromol/L, 10 micromol/L and 20 micromol/L STAT1-alpha AS treatment (P < 0.01). The expression of CIITA mRNA in the S groups was higher than that in the AS groups (P < 0.01), but there was no significant difference between the S group and the control group. The expression of HLA-DR antigen was significantly inhibited by STAT1-alpha AS, and the expression level of HLA-DR protein in the AS group was about 64.3% of that in the control group (P < 0.01), while there was no significant difference in HLA-DR expression between the S group and the control group. The changes in HLA-DR expression were similar to those in CIITA expression after STAT1-alpha AS treatment. It is concluded that CIITA expression is positively correlated with HLA-DR expression, and was detectable earlier than that of latter after IFN-gamma incubation. Stat1-alpha antisense oligonucleotides may have a sequence-specific inhibiting effect on the expression of CIITA and HLA-DR antigen after IFN-gamma incubation in vitro culture, and can prevent T lymphocyte activation. CIITA may play an important role in pathogenesis of transplantation immunity.
