Expansion of circulating Foxp3+CD25bright CD4+ T cells during specific venom immunotherapy

Pereira-Santos, Maria Conceição; Baptista, António P.; Melo, Alcinda Campos; Alves, Ronaldo; Soares, Rui; Pedro, Elisa; Barbosa, Manuel Pereira; Victorino, Rui M. M.; Sousa, Ana E.

doi:10.1111/j.1365-2222.2007.02887.x

Cited by 65 publications

(61 citation statements)

References 38 publications

(60 reference statements)

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“…This finding is in keeping with a study by Pereira-Santos et al, who showed a significant increase in FoxP3 + T cells 6 and 12 months after venom immunotherapy in adolescents and adults (mean age 47, range 16-65) [62].…”

Section: Discussionsupporting

confidence: 93%

Tolerance induction after specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A in children

Rosewich

Schulze

Eickmeier

et al. 2010

Clinical and Experimental Immunology

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SummarySpecific immunotherapy (SIT) is a well-established and clinically effective treatment for allergic diseases. A pollen allergoid formulated with the T helper type 1 (Th1)-inducing adjuvant monophosphoryl lipid A (MPL) facilitates short-term SIT. Little is known about mechanisms of tolerance induction in this setting. In a prospective study, 34 patients allergic to grass pollen (25 male, nine female, median age 10·2 years) received a total of 44 SIT courses (20 in the first, 24 in the second) with MPL-adjuvanted pollen allergoids. Immunogenicity was measured by levels of specific immunoglobulin G (IgGgrass) and IgG4grass by antibody blocking properties on basophil activation, and by induction of CD4 + , CD25 + and forkhead box P3 (FoxP3 + ) regulatory T cells (Treg). Specific IgG and IgG4 levels increased only slightly in the first year of SIT. In the second year these changes reached significance (P < 0·0001). In keeping with these findings, we were able to show an increase of Treg cells and a decreased release of leukotrienes after the second year of treatment. In the first year of treatment we found little evidence for immunological changes. A significant antibody induction was seen only after the second course of SIT. Short-course immunotherapy with pollen allergoids formulated with the Th1-inducing adjuvant MPL needs at least two courses to establish tolerance.

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Section: Discussionsupporting

confidence: 93%

Tolerance induction after specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A in children

Rosewich

Schulze

Eickmeier

et al. 2010

Clinical and Experimental Immunology

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“…3, 5b, 6b). Several reports have shown that Foxp3-positive cells and/or IL-10-producing cells are induced by immunotherapy and that IL-10 is crucial for downregulation of inflammatory Th2 responses [6,8,18,19]. Foxp3-expressing CD4 + CD25 + cells are reported to be induced in the nasal mucosa after immunotherapy, and local induction of iTregs is suggested to be important to suppress local inflammation during pollen season [7].…”

Section: Discussionmentioning

confidence: 99%

“…Foxp3-expressing CD4 + CD25 + cells are reported to be induced in the nasal mucosa after immunotherapy, and local induction of iTregs is suggested to be important to suppress local inflammation during pollen season [7]. Furthermore, the basal frequencies of Tregs defined as CD4 + CD25 bright Foxp3 + cells in the peripheral blood of patients with severe allergic reactions to insect stings were reported to be lower than in individuals without a history of allergic diseases, and the Treg population was upregulated to a level comparable to that of nonallergic subjects after immunotherapy against bee venom [6]. …”

Section: Discussionmentioning

confidence: 99%

“…It was reported that the number of Tregs, namely CD25 bright and/or Foxp3 + CD4 + T cells, was significantly increased during specific immunotherapy against bee venom [6]. It has also been reported that Foxp3 + CD25 + and Foxp3 + CD4 + cell levels were significantly increased in the nasal mucosa of patients receiving immunotherapy treatment with grass pollen [7].…”

Section: Introductionmentioning

confidence: 98%

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The Induced Regulatory T Cell Level, Defined as the Proportion of IL-10+Foxp3+ Cells among CD25+CD4+ Leukocytes, Is a Potential Therapeutic Biomarker for Sublingual Immunotherapy: A Preliminary Report

Fujimura

Yonekura²,

Taniguchi³

et al. 2010

Int Arch Allergy Immunol

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Background:Japanese cedar (Cryptomeria japonica) pollinosis is one of the most prevalent allergies in Japan. Recently, two reports described the positive effects of sublingual immunotherapy (SLIT) against Japanese cedar pollinosis. However, the therapeutic biomarkers for SLIT are still unclear. We performed this unblinded, nonrandomized, open-label study to identify therapeutic biomarkers for SLIT against Japanese cedar pollinosis. Methods:We performed an open-label study during one pollinosis season in 2007, enrolling 19 patients from in-house volunteers suffering from Japanese cedar pollinosis. Peripheral blood was obtained from all participants before SLIT treatment as well as before and after the pollen season. The plasma levels of an immunoglobulin specific to a major allergen (Cry j 1) were determined. We analyzed the induction of regulatory T cells (iTregs), namely IL-10⁺Foxp3⁺ cells in CD25⁺CD4⁺ leukocytes, by flow cytometry. The Th2-type responses were analyzed by cytokine production from peripheral blood mononuclear cells after stimulation with Cry j 1. Clinical symptoms were estimated using a quality of life questionnaire in the middle of the pollen season. Results: The difference in numbers of iTregs between the medium-only control cell culture and cells stimulat- ed with Cry j 1 was significantly decreased in the non-SLIT group but was unchanged in the SLIT group after the pollen season. The subgroup of the SLIT group with increased iTregs showed more attenuated Th2-type cytokine profiles, and symptom scores in the subgroup with increased iTregs were significantly lower than those in the subgroup with decreased iTregs. Conclusion:The antigen-specific iTreg level is a potential therapeutic biomarker that correlates with clinical pollinosis symptoms and may be involved in the therapeutic mechanisms of SLIT.

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“…Bussmann et al [35 ]have reported that IL-10 serum levels increase from the second day of the build-up phase during bee VIT. Moreover, Pereira-Santos et al [36 ]have remarked that a nonresponsive state is established in allergen-specific T cells due to the direct suppressive effects of IL-10 after 28 days of VIT. Two forms of OPN, i.e.…”

Section: Discussionmentioning

confidence: 99%

Increased Osteopontin Levels in Children Undergoing Venom Immunotherapy May Serve as a Marker of Clinical Efficacy

Yavuz¹,

Soyer²,

Şekerel³

et al. 2014

Int Arch Allergy Immunol

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Background: Venom immunotherapy (VIT) has its effect by modulating various mediators resulting in immune tolerance. The aim of this study was to measure changes in plasma osteopontin (OPN) and serum basal tryptase (sBT) levels over the course of 1 year of VIT in children with venom allergy. Methods: Children who suffered from a large local reaction (LLR) or a systemic reaction (SR) after insect stings were included along with control subjects. Measurements were performed before the initiation of VIT and 6 and 12 months after it had been started. Results: A total of 58 children (24 with SR, 18 with LLR and 16 control subjects) with a median age of 9.5 years (range 6.7-12.8) were enrolled. The plasma OPN levels of patients with LLR [median 1,477 ng/ml, interquartile range (IQR) 1,123-1,772] were significantly higher than patients with SR (882 ng/ml, 579-1,086; p < 0.001) and healthy control subjects (1,015 ng/ml, 815-1,203; p = 0.002). A significant increase in plasma OPN levels in children was determined after the 1-year VIT. The sBT levels of children with SR (4.1 ng/ml, 3.6-5.8) were significantly higher than children with LLR (3.1 ng/ml, 2.5-4.0) and control subjects (3.0 ng/ml, 2.9-3.8; p = 0.001). There was no significant change in the sBT levels of the patients after the 1-year VIT. Conclusions: The results of our study showed higher baseline levels of OPN in children with LLR compared to control subjects and children with SR. In children with SR, OPN levels were increased after the 1-year VIT. Our results may suggest a possible association between OPN and successful VIT in children.

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Expansion of circulating Foxp3⁺CD25^bright CD4⁺ T cells during specific venom immunotherapy

Abstract: VIT is associated with a progressive expansion of circulating regulatory T cells, supporting a role for these cells in tolerance induction.

Cited by 65 publications

References 38 publications

Tolerance induction after specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A in children

Tolerance induction after specific immunotherapy with pollen allergoids adjuvanted by monophosphoryl lipid A in children

The Induced Regulatory T Cell Level, Defined as the Proportion of IL-10<sup>+</sup>Foxp3<sup>+</sup> Cells among CD25<sup>+</sup>CD4<sup>+</sup> Leukocytes, Is a Potential Therapeutic Biomarker for Sublingual Immunotherapy: A Preliminary Report

Increased Osteopontin Levels in Children Undergoing Venom Immunotherapy May Serve as a Marker of Clinical Efficacy

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