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Interleukin-2 inhibits the interleukin-4-induced human IgE and IgG4 secretion in vivo
H L Spiegelberg1, R J Falkoff, R D O'Connor
1Department of Immunology, Research Institute of Scripps Clinic, La Jolla, CA.
Insights
Interleukin-2 (IL-2) suppresses immunoglobulin E (IgE) and IgG4 secretion in human B cells, acting later in culture compared to interferon-gamma (IFN-gamma). This research explores immune regulation in B cell responses.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- Interleukin-4 (IL-4) stimulates IgE and IgG4 secretion by B cells.
- Understanding the regulation of B cell antibody secretion is crucial for immune system research.
Purpose of the Study:
- To investigate the effect of interleukin-2 (IL-2) on IL-4-induced IgE and IgG4 secretion by human B cells.
- To compare the inhibitory mechanisms of IL-2 and interferon-gamma (IFN-gamma) on B cell antibody production.
Main Methods:
- Peripheral blood mononuclear cells (PBMCs) from healthy and atopic donors were cultured with IL-4 and varying concentrations of IL-2 for 10 days.
- Antibodies against IL-2 and its receptor (anti-TAC) were used to confirm IL-2's role.
- Timing of IL-2 and IFN-gamma addition was varied to assess their inhibitory effects.
Main Results:
- Both native and recombinant IL-2 dose-dependently inhibited IL-4-induced IgE and IgG4 secretion in cells from all donors.
- IL-2's inhibitory effect was more pronounced when added later in the culture (days 4-5) compared to early addition (days 1-2).
- IFN-gamma showed an early inhibitory effect, contrasting with IL-2's later action, suggesting distinct mechanisms.
Conclusions:
- IL-2 acts as an antagonist to IL-4-induced IgE and IgG4 secretion in human B cells, with a late inhibitory effect.
- IL-2 and IFN-gamma exhibit different temporal mechanisms in antagonizing IL-4's effect on B cell antibody production.
- These findings contribute to understanding immune modulation and potential therapeutic targets in allergic diseases.
Abstract:
The effect of interleukin-2 (IL-2) on IL-4-induced IgE and IgG4 secretion by B cells in peripheral blood mononuclear cell (PBMC) preparations from non-atopic healthy humans and atopic dermatitis patients was investigated. PBMC were cultured at an optimal concentration of recombinant IL-4 with or without addition of IL-2 for 10 days. Native and recombinant IL-2 inhibited the IL-4-induced IgE and IgG4 secretion in a dose-dependent manner by cells from both normal and atopic donors. Rabbit antibodies to IL-2 or to the monoclonal anti-IL-2 receptor antibody anti-TAC reversed the IL-2 effect. Culturing cells with IL-4 and IL-2 for 1 or 2 days only slightly suppressed the IgE and IgG4 secretion whereas addition of IL-2 to IL-4 containing cultures on day 4 or 5 inhibited the IgE and IgG4 secretion more effectively. This is in contrast to interferon-gamma (IFN-gamma) which inhibited the IL-4 induced IgE and IgG4 secretion when added for the first 24 or 48 h but had no effect when added on days 4 or 5. The data demonstrate that both IL-2 and IFN-gamma act as antagonists in the IL-4-induced IgE and IgG4 secretion by human B cells; while IL-2 appears to inhibit relatively late in culture, IFN-gamma has an early inhibitory effect, suggesting that the two lymphokines inhibit the IL-4 effect by different mechanisms.
