BACKGROUND: Indoleamine 2,3-dioxygenase (IDO) is a tryptophan (TRP)-catabolizing enzyme with regulatory effects on T cells. T cell inhibition is achieved through both TRP depletion and TRP metabolite accumulation in specific local tissue microenvironments. The expression of IDO activity by different types of antigen-presenting cells (APCs) has been shown to play a role in many instances of immunoregulation and tolerance induction. Induction of IDO after the engagement of the high-affinity receptor for IgE, FcepsilonRI, on atopic monocytes has been suggested to regulate T cell responses in atopic disorders. Interleukin-10 (IL-10), a cytokine known for its down-regulatory functions in the immune system, has recently been associated with the stable expression of IDO in mature tolerogenic dendritic cells. OBJECTIVE: This study was devised to understand the role of systemic IDO and IL-10 in the prevention of clinical apparent allergy. METHODS: The concentration of TRP and the break-down product kynurenine were measured by high-performance liquid chromatography in- and off-season in sera from patients with seasonal allergic rhinitis (n=12) and from clinically asymptomatic atopic patients sensitized to specific aeroallergens (n=12). Non-atopic (NA) individuals (n=12) served as control. The concentration of plasma IL-10 was determined in parallel from these donors by ELISA in- and off-season. RESULTS: In clinically unresponsive but aeroallergen-sensitized atopic individuals significantly higher systemic activity of IDO and increased plasma IL-10 levels were found during allergen exposure but not off-season compared to symptomatic atopic individuals with allergic rhinitis and NA individuals. CONCLUSION: Enhanced systemic IDO activity as well as increased systemic levels of IL-10 may contribute to the containment of allergic T cell responses and could be involved in the maintenance of a state of clinical unresponsiveness.
BACKGROUND:Indoleamine 2,3-dioxygenase (IDO) is a tryptophan (TRP)-catabolizing enzyme with regulatory effects on T cells. T cell inhibition is achieved through both TRP depletion and TRP metabolite accumulation in specific local tissue microenvironments. The expression of IDO activity by different types of antigen-presenting cells (APCs) has been shown to play a role in many instances of immunoregulation and tolerance induction. Induction of IDO after the engagement of the high-affinity receptor for IgE, FcepsilonRI, on atopic monocytes has been suggested to regulate T cell responses in atopic disorders. Interleukin-10 (IL-10), a cytokine known for its down-regulatory functions in the immune system, has recently been associated with the stable expression of IDO in mature tolerogenic dendritic cells. OBJECTIVE: This study was devised to understand the role of systemic IDO and IL-10 in the prevention of clinical apparent allergy. METHODS: The concentration of TRP and the break-down product kynurenine were measured by high-performance liquid chromatography in- and off-season in sera from patients with seasonal allergic rhinitis (n=12) and from clinically asymptomatic atopic patients sensitized to specific aeroallergens (n=12). Non-atopic (NA) individuals (n=12) served as control. The concentration of plasma IL-10 was determined in parallel from these donors by ELISA in- and off-season. RESULTS: In clinically unresponsive but aeroallergen-sensitized atopic individuals significantly higher systemic activity of IDO and increased plasma IL-10 levels were found during allergen exposure but not off-season compared to symptomatic atopic individuals with allergic rhinitis and NA individuals. CONCLUSION: Enhanced systemic IDO activity as well as increased systemic levels of IL-10 may contribute to the containment of allergic T cell responses and could be involved in the maintenance of a state of clinical unresponsiveness.
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