The T Cell Response to Major Grass Allergens Is Regulated and Includes IL-10 Production in Atopic but Not in Non-Atopic Subjects

Abstract

Background: The incidence of allergic diseases is increasing in industrialized countries and the immunological mechanisms leading to tolerance or allergy are poorly understood. Cytokines with suppressive abilities and CD4⁺CD25⁺ regulatory T cells have been suggested to play a central role in allergen-specific responses. The aim was to determine whether major grass allergens induce production of suppressive cytokines in allergic and healthy subjects and to examine the inhibitory effect of these cytokines on allergic responses. Methods: Peripheral blood mononuclear cells (PBMCs) were isolated from healthy and grass-allergic donors and stimulated with the major grass allergens Phl p 1 or Phl p 5. The effects of endogenous IL-10 and/or TGF-β on proliferation and cytokine production were determined by use of blocking antibodies. In addition, the number of CD4⁺CD25⁺ T cells and their expression of chemokine receptors were investigated by flow cytometry. Results: Phl p 1 and Phl p 5 induced IL-10 production, which down-regulated proliferation and cytokine production, in PBMC cultures from atopic but not from non-atopic donors. Comparable frequencies of CD4⁺CD25⁺ T cells were present in PBMCs in the two groups, but fewer cells from atopic donors were CD4⁺CD25⁺CCR4⁺ and more cells were CD4⁺CD25⁺CLA⁺ compared to healthy donors. Conclusion:Allergen-specific responses of grass allergic patients but not in non-atopic subjects are influenced by regulatory cytokines produced in response to the important allergens. Differences in CD4⁺CD25⁺ T cell expression of chemokine receptors in allergic compared to non-atopic donors could suggest that the homing of CD4⁺CD25⁺ T cells is important for the regulation of allergen-specific responses.

Human Leukocyte Antigen-G and Regulatory T Cells during Specific Immunotherapy for Pollen Allergy

“…When a blocking antibody against the IL-10 receptor was added to the specific allergen-stimulated PBMC cultures, the level of IL-2 increased significantly, and the level of IL-10 showed an increasing trend compared to the cultures that were treated with an isotype antibody control (p = 0.018 and p = 0.237, respectively, Wilcoxon). These data are in agreement with a previously published study [9]. Furthermore, IL-10 can block the production of IL-2 in an indirect manner [51].…”

“…However, in vivo and in vitro induction of Tregs in patients suffering from pollen allergies who have received SIT is a controversial subject. Different in vivo experiments have shown that the frequencies of CD4 + CD25 + CD127 low/- Tregs do not differ between the initiation and maintenance phases of SIT and that, furthermore, similar frequencies of CD4 + CD25 + Tregs can be found in healthy nonatopic controls and atopic patients [9,36]. However, other in vitro experiments have found a significant increase in the frequency of CD4 + CD25 + Foxp3 + /CD127 low Tregs in allergen-stimulated cultures of PBMCs collected prior to and after 24 months of SLIT [37].…”

“…Furthermore, Tregs have been suggested to suppress allergic effector cells such as mast cells and basophils, as well as the production of allergen-specific IgE from B cells, while promoting the production of allergen-specific IgG 4 to function as a blocking antibody [4]. However, results from other studies suggest opposite effects of Tregs with regard to allergy and related treatment [9,10]. …”

“…Studies have shown that CCR4 is involved in the antigen-specific trafficking of T H 2 cells and in T H 2-polarized allergic immune responses [15,16]. However, there are conflicting views regarding the role of CCR4 in allergic diseases [9,17]. Allergic individuals express lower levels of the T H 1-chemokine receptor chemokine (C-X-C) motif receptor 3 (CXCR3).…”

Differences in Systemic and Skin Migrating-Specific CD4⁺ T Cells in Papular Urticaria by Flea Bite

“…The association of IL-10-secreting cells and allergy is controversial [26], but PBMCs from grass-allergic patients have an IL-10 response not found in healthy individuals [27]. In vitro, neutralization of IL-10 increased proinflammatory cytokine secretion [28] and allergen-pulsed DCs in the presence of IL-10-induced regulatory cells [29].…”