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Immune Responses to Inhalant Allergens

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      Abstract

      This overview describes the nature of the immune responses induced by the inhalation of allergens. There is a dichotomy in that B cells have multiple mechanisms that limit the amount of immunoglobulin E (IgE) antibody production, whereas T-cell responses are large even in nonallergic subjects. With the possible exception of responses to cat allergen, however, T cells from nonallergic subjects have limited effector function of helping IgG antibody, and in house-dust mite allergy, this declines with age. Regulation by interleukin 10 (IL-10)-producing cells and CD25 + T-regulatory cells has been proposed, but critically, there is limited evidence for this, and many studies show the highest IL-10 production by cells from allergic subjects. Recent studies have shown the importance of nonlymphoid chemokines thymic stromal lymphopoietin and IL-27, so studying responses in situ is critical. Most sources of allergens have 1 or 2 dominant allergens, and for house-dust mite, it has been shown that people have a predictable responsiveness to high-, mid-and poor-IgE-binding proteins regardless of the total size of their response. This allergen hierarchy can be used to design improved allergen preparations and to investigate how antiallergen responses are regulated.

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      Immune Responses in Healthy and Allergic Individuals Are Characterized by a Fine Balance between Allergen-specific T Regulatory 1 and T Helper 2 Cells

      The mechanisms by which immune responses to nonpathogenic environmental antigens lead to either allergy or nonharmful immunity are unknown. Single allergen-specific T cells constitute a very small fraction of the whole CD4+ T cell repertoire and can be isolated from the peripheral blood of humans according to their cytokine profile. Freshly purified interferon-γ–, interleukin (IL)-4–, and IL-10–producing allergen-specific CD4+ T cells display characteristics of T helper cell (Th)1-, Th2-, and T regulatory (Tr)1–like cells, respectively. Tr1 cells consistently represent the dominant subset specific for common environmental allergens in healthy individuals; in contrast, there is a high frequency of allergen-specific IL-4–secreting T cells in allergic individuals. Tr1 cells use multiple suppressive mechanisms, IL-10 and TGF-β as secreted cytokines, and cytotoxic T lymphocyte antigen 4 and programmed death 1 as surface molecules. Healthy and allergic individuals exhibit all three allergen-specific subsets in different proportions, indicating that a change in the dominant subset may lead to allergy development or recovery. Accordingly, blocking the suppressor activity of Tr1 cells or increasing Th2 cell frequency enhances allergen-specific Th2 cell activation ex vivo. These results indicate that the balance between allergen-specific Tr1 cells and Th2 cells may be decisive in the development of allergy.
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        Foxp3 in control of the regulatory T cell lineage.

        Foxp3, an X chromosome-encoded forkhead transcription factor family member, is indispensable for the differentiation of regulatory T cells. These cells have a vital role in preventing autoimmunity and pathology inflicted by uncontrolled immune responses to infections. Deficiency or mutation in Foxp3 in humans and mice leads to an early onset, highly aggressive and fatal autoimmune disease affecting various tissues. Here, we review recent advances in our understanding of the Foxp3-dependent molecular and functional program and the role of Foxp3 in regulatory T cell biology.
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          IL-10 and TGF-beta cooperate in the regulatory T cell response to mucosal allergens in normal immunity and specific immunotherapy.

          The regulation of normal and allergic immune responses to airborne allergens in the mucosa is still poorly understood, and the mechanism of specific immunotherapy (SIT) in normalizing the allergic response to such allergens is currently not clear. Accordingly, we have investigated the immunoregulatory mechanism of both normal and allergic responses to the major house-dust mite (HDM) and birch pollen allergens--Dermatophagoides pteroynyssinus (Der p)1 and Bet v 1, respectively--as well as the immunologic basis of SIT to HDM in rhinitis and asthma patients. In normal immunity to HDM and birch pollen, an allergen-specific peripheral T cell suppression to Der p 1 and Bet v 1 was observed. The deviated immune response was characterized by suppressed proliferative T cell and Th1 (IFN-gamma) and Th2 (IL-5, IL-13) cytokine responses, and increased IL-10 and TGF-beta secretion by allergen-specific T cells. Neutralization of cytokine activity showed that T cell suppression was induced by IL-10 and TGF-beta during SIT and in normal immunity to the mucosal allergens. In addition, SIT induced an antigen-specific suppressive activity in CD4(+) CD25(+) T cells of allergic individuals. Together, these results demonstrate a deviation towards a regulatory/suppressor T cell response during SIT and in normal immunity as a key event for the healthy immune response to mucosal antigens.
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            Author and article information

            Affiliations
            [1 ]Centre for Child Health Research, University of Western Australia, Telethon Institute for Health Research, Western Australia
            Contributors
            Journal
            World Allergy Organ J
            World Allergy Organ J
            The World Allergy Organization Journal
            World Allergy Organization
            1939-4551
            June 2008
            15 June 2008
            : 1
            : 6
            : 89-95
            23282404
            3650949
            1939-4551-1-6-89
            10.1097/WOX.0b013e3181788324
            Copyright ©2008 World Allergy Organization; licensee BioMed Central Ltd.

            This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

            Categories
            Review Article

            Immunology

            allergens, immunoregulation, ige antibody, igg antibody, t cells, b cells

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