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Suppression of human monocyte function against Candida albicans by autologous IL-2-induced lymphokine-activated
S Wei1, D Serbousek, S McMillen
1University of South Florida College of Medicine, Department of Medical Microbiology, Tampa 33612.
Insights
Interleukin-2-induced lymphokine-activated killer (LAK) cells suppress human monocyte antifungal activity. Cytokine priming, particularly with granulocyte/macrophage colony-stimulating factor (GM-CSF), enhances this monocyte susceptibility to LAK cell inhibition.
Area of Science:
- Immunology
- Cellular Biology
- Infectious Diseases
Background:
- Lymphokine-activated killer (LAK) cells, induced by Interleukin-2 (IL-2), can lyse monocytes.
- The functional consequences of LAK cell interaction with monocytes, especially in the context of fighting pathogens, remain incompletely understood.
- Monocytes play a crucial role in the innate immune response against opportunistic infections like Candida albicans.
Purpose of the Study:
- To investigate the functional impact of human monocytes on Candida albicans after exposure to autologous LAK cells.
- To determine how cytokine priming of monocytes influences their susceptibility to LAK cell-mediated inhibition.
- To elucidate the role of LAK cells in regulating monocyte function in the context of immune responses.
Main Methods:
- Development of a sensitive radiolabel assay using [3H]glucose incorporation to quantify Candida growth inhibition by monocytes.
- Incubation of human monocytes with autologous LAK cells for short periods (2-6 hours).
- Culture of monocytes with specific cytokines, including granulocyte/macrophage colony-stimulating factor (GM-CSF), Interleukin-3 (IL-3), and Interferon-gamma (IFN-γ), followed by exposure to LAK cells or Natural Killer (NK) cells.
Main Results:
- Short-term exposure to LAK cells significantly suppressed the ability of monocytes to control Candida albicans growth.
- Monocytes pre-cultured with GM-CSF or IL-3 exhibited further suppression of antifungal function after LAK cell interaction, with GM-CSF effects being time- and dose-dependent.
- GM-CSF-primed monocytes showed relative resistance to inhibition by NK cells, whereas IFN-γ pre-culture protected monocytes from LAK cell-induced inhibition.
Conclusions:
- IL-2-induced LAK cells possess the capacity to inhibit monocyte antifungal functions.
- The susceptibility of monocytes to LAK cell-mediated inhibition is modulated by their cytokine-induced differentiation state.
- These findings suggest a regulatory role for LAK cells in monocyte function, with implications for immune responses to pathogens.
Abstract:
We have previously reported that IL-2-induced lymphokine-activated killer (LAK) cells have the capacity to lyse autologous and allogeneic monocytes. To understand the biologic significance of this interaction, we investigated the function of human monocytes against the opportunistic pathogen, Candida albicans, subsequent to a short exposure to autologous LAK cells. A highly sensitive radiolabel assay, which makes use of the incorporation of [3H]glucose into residual Candida after their incubation with monocytes, was developed to measure antifungal activity. Cultured monocytes, after 2 to 6 h exposure to LAK cells, were found to be substantially suppressed in their ability to control fungal growth. Moreover, monocytes cultured in the presence of granulocyte/macrophage (GM)-CSF or IL-3, were even more suppressed in function after a short incubation with LAK cells. The effect of GM-CSF was both time and dose dependent, with peak susceptibility induced after 4 days of culture with as little as 10 U/ml of the cytokine. These GM-CSF-cultured monocytes, however, were relatively resistant to inhibition by freshly isolated large granular lymphocytic NK cells. Therefore, IL-2 induces in large granular lymphocytic cells the capacity to inhibit monocyte function. In contrast to GM-CSF and IL-3, IFN-gamma was found to have a protective effect on monocytes, because monocytes cultured 4 days in IFN-gamma were not significantly inhibited by LAK cells. These results indicate that LAK cells may be involved in regulation of monocyte function and suggest that the state of differentiation induced by different cytokines may dictate the level of control of the monocytes by LAK cells.