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Effect of diisopropylfluorophosphate on the antibody response
1Operational Medicine Section, Defence and Civil Institute of Environmental Medicine, Downsview, Ontario, Canada.
Abstract:
The impact of the in-vivo administration of diisopropylfluorophosphate (DFP) on the antibody response in mice was examined. The antigen-specific plaque-forming cell (PFC) response of mice injected with DFP (4 mg/kg) at the time of immunization with a macrophage-dependent T-cell antigen, trinitrophenylated keyhole limpet hemocyanin (TNP-KLH) or sheep red blood cells (SRBC), was significantly depressed. In contrast, the injection of a similar dose of DFP had no effect on the PFC response of mice immunized with a macrophage-independent B-cell antigen, lipopolysaccharide (LPS). This differential effect suggests a possible detrimental effect of DFP on cells involved in antigen processing and/or presentation which are required for the antibody response to SRBC and TNP-KLH. These results, however, do not exclude T cells as a possible target and the cellular targets of DFP action remain to be established. The DFP-mediated depression of the PFC response to SRBC was still evident when DFP was given as early as 1 day before, but not 1 day after, the injection of antigen, suggesting that DFP may well affect an early event of the antibody response. For the secondary TNP-specific IgM PFC response, a significant depression was observed only when DFP was administered at the time of antigen challenge. The injection of DFP at the time of antigen priming, however, was effective in depressing the IgG, but not the IgM, PFC response. Therefore, DFP may also interfere with the generation of antigen-specific memory cells for the secondary IgG response.
Insights
Diisopropylfluorophosphate (DFP) significantly depresses antibody production in mice, particularly for T-cell dependent antigens. This suggests DFP impacts early immune responses and potentially memory cell generation.
Area of Science:
- Immunology
- Pharmacology
Background:
- Diisopropylfluorophosphate (DFP) is an organophosphate compound.
- The effects of DFP on the adaptive immune system, specifically antibody production, require further elucidation.
Purpose of the Study:
- To investigate the impact of in-vivo diisopropylfluorophosphate (DFP) administration on the antibody-producing cell response in mice.
- To determine if DFP affects T-cell dependent and T-cell independent antibody responses differently.
Main Methods:
- Mice were immunized with either macrophage-dependent antigens (TNP-KLH, SRBC) or a macrophage-independent antigen (LPS).
- Diisopropylfluorophosphate (DFP) was administered at various time points relative to antigen exposure.
- Antigen-specific plaque-forming cell (PFC) responses were quantified to assess antibody production.
Main Results:
- DFP significantly depressed the PFC response to T-cell dependent antigens (TNP-KLH, SRBC) but not to the T-cell independent antigen (LPS).
- DFP administration one day before antigen injection, but not one day after, reduced the PFC response to SRBC, indicating an effect on early immune events.
- DFP administered during antigen priming suppressed the secondary IgG PFC response but not the IgM PFC response, suggesting interference with memory cell generation for IgG.
Conclusions:
- DFP exhibits a differential effect on antibody production, primarily impacting T-cell dependent responses.
- DFP appears to interfere with early stages of the antibody response and may also affect the generation of antigen-specific memory cells for secondary IgG responses.
- The precise cellular targets of DFP's immunomodulatory effects warrant further investigation.