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Published on: January 15, 2011
[Study on the up-regulation of B7 molecules expression and immunogenicity of acute leukemia cells induced by
1First Affiliated Hospital, Medical College, Zhejiang University, Hangzhou 310003, China.
Insights
Interleukin 7 (IL-7) enhances B7 molecule expression on acute leukemia (AL) cells, increasing their immunogenicity. This IL-7 treatment stimulates T-cell proliferation and interferon-gamma production, suggesting a potential therapeutic role in leukemia immunotherapy.
Area of Science:
- Immunology
- Hematology
- Cancer Research
Background:
- Acute leukemia (AL) cells typically exhibit low expression of B7-1 and B7-2 molecules, which are crucial for T-cell activation.
- The role of cytokines, such as interleukin 7 (IL-7), in modulating the immunogenicity of leukemia cells remains an area of active investigation.
Purpose of the Study:
- To investigate the impact of IL-7 on the expression of B7 molecules (B7-1 and B7-2) on acute leukemia cells.
- To evaluate the effect of IL-7-treated leukemia cells on the immunogenicity and T-cell stimulatory capacity.
Main Methods:
- Flow cytometry (FACScan) was used to quantify B7 molecules on leukemia cells.
- Reverse transcription-polymerase chain reaction (RT-PCR) assessed B7-1 and B7-2 mRNA levels.
- MTT assays and enzyme-linked immunosorbent assays (ELISA) measured peripheral blood mononuclear cell (PBMNC) proliferation and interferon-gamma (IFN-γ) secretion, respectively.
Main Results:
- Fresh AL cells showed weak B7-1 and B7-2 expression.
- IL-7 significantly upregulated B7 molecules and their corresponding mRNAs on leukemia cells in a time-dependent manner.
- IL-7 treated leukemia cells enhanced PBMNC proliferation and IFN-γ production, with inhibition observed using anti-B7-1 and W6/32 antibodies.
Conclusions:
- IL-7 effectively enhances B7 molecule expression on acute leukemia cells, thereby increasing their immunogenicity.
- IL-7 treated leukemia cells demonstrate an enhanced capacity to stimulate allogeneic PBMNC proliferation and IFN-γ secretion.
- These findings suggest that IL-7 may hold potential for augmenting anti-leukemia immune responses.
Objective:
To investigate the effects of interleukin 7 (IL-7) on B7 molecules expression and immunogenicity of acute leukemia (AL) cells.
Methods:
The B7 molecules expression on fresh acute leukemia cells and on the IL-7 exposed leukemia cells was detected by FACScan cytometer. B7-1 and B7-2 mRNA in IL-7 treated HL-60 cells were detected by reverse transcription-PCR (RT-PCR). The stimulation of proliferation of allogeneic peripheral blood mononuclear cells (PBMNC) by IL-7 treated leukemia cells was detected by MTT method. The level of interferon-gamma (IFN-gamma) secreted by the stimulated PBMNC was determined using enzyme-linked immunosorbent assays (ELISA). The blocking experiments were performed using monoclonal antibodies against B7-1, B7-2 and W6/32.
Results:
B7-1 was weakly expressed in three, whereas B7-2 did in only one of eleven AL patients. IL-7 significantly enhanced B7 molecules expression on AL cells in a time-dependent manner. Furthermore, IL-7 could induce higher expression of B7-1 and B7-2 mRNAs on HL-60 cells. IL-7 treated leukemia cells could stimulate PBMNC proliferation and promote their IFN-gamma production. Anti-B7-1 and anti W6/32 but not anti-B7-2 monoclonal antibodies significantly inhibited the stimulated PBMNC proliferation and IFN-gamma secretion.
Conclusion:
Fresh AL cells express low level of B7-1 and B7-2 molecules. IL-7 enhances the B7 molecules expression on AL cells. The IL-7-treated leukemia cells can significantly stimulate the proliferation of allogeneic PBMNC and induce their IFN gamma secretion.
