The identical effects of B7-1 and B7-2 on regulation of human IL-2 gene transcription factors NF-kappa B and AP-1.
- Author:
Xiao-Yan KE
1
;
John GRIBBEN
;
Jing WANG
;
De-Bing WANG
Author Information
1. Department of Hematology, The Third Hospital, Peking University, Beijing 100083, China. xiaoyank@yahoo.com
- Publication Type:Journal Article
- MeSH:
3T3 Cells;
Animals;
Antigens, CD;
physiology;
B7-1 Antigen;
physiology;
B7-2 Antigen;
CD28 Antigens;
physiology;
Gene Expression Regulation;
Humans;
Interferon-gamma;
genetics;
Interleukin-2;
genetics;
Interleukin-4;
genetics;
Lymphocyte Culture Test, Mixed;
Membrane Glycoproteins;
physiology;
Mice;
NF-kappa B;
metabolism;
RNA, Messenger;
analysis;
Transcription Factor AP-1;
metabolism
- From:
Journal of Experimental Hematology
2002;10(6):512-518
- CountryChina
- Language:Chinese
-
Abstract:
To detect effects of B7 co-stimulation on cytokines, especially on IL-2 mRNA and transcription factors NF-kappa B and AP-1, antiB7-1 McAb, antiB7-2 McAb and C TLA-4 Ig were added into mixture lymphocyte reaction (MLR) system to block B7/C D28 signal transduction, IL-2 mRNA and IL-4 mRNA were determined by using competitive PCR and IFN-gamma mRNA by using semi-quantitative PCR. MHC class II molecules and B7 transfectants were used to stimulate CD28(+) T cell, effects of B7 on NF-kappa B and AP-1 were detected by DNA-protein binding assay. The results showed that IL-2, IL-4 and IFN-gamma mRNA were significantly lower when blockade of B7-2 in MLR than blockade of B7-1. Synergistic effects could be seen with combination of two or three antibodies. One to six hours after MLR, tDR7 alone induced NF-kappa B binding activity; cotransfecting B7 no significantly difference at early time point. After 6 hours, induction of tDR7 was decreased whereas B7 prolonged the induction of NF-kappa B till 72 hours. tDR7 alone also upregulated AP-1 binding activity, on the contrary to NF-kappa B, co-transfecting B7-1 and B7-2 decreased AP-1 binding activity within 24 hours. But during 48 - 72 hours, B7 also prolonged the AP-1 binding activity. It is concluded that after MLR, B 7 increased IL-2 secretion by decreasing the degradation of IL-2 mRNA and upregulating IL-2 transcription factors. B7 also induced several kinds of cytokines secretion. Effects of B7-1 and B7-2 had no significant difference on transcription factors. It is suggested that the different functions between B7-1 and B7-2 maybe related to the difference of cell expression and kinetics. To study the molecular mechanism of B7 mediated T cell immune tolerance can help us to design a better clinic schema to prevent transplantation rejection and GVHD.
