T-Cell Regulatory Mechanisms in Specific Immunotherapy

Jutel, Marek; Akdiş, Cezmi A.

doi:10.1159/000155000

Cited by 45 publications

(30 citation statements)

References 189 publications

(225 reference statements)

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“…This altered inflammatory milieu could then be expected to favor increased Treg numbers and/or function. Similar effects have been seen after allergen immunotherapy [32] which has no reported effects on endogenous CS levels. Further, our current studies were performed on PBMC from normal individuals rather than from those with allergic or autoimmune diseases who have a known Treg deficiency and/or dysfunction.…”

Section: Discussionsupporting

confidence: 72%

Immunomodulatory Effects of in vitroStress Hormones on FoxP3, Th1/Th2 Cytokine and Costimulatory Molecule mRNA Expression in Human Peripheral Blood Mononuclear Cells

Xiang¹,

Marshall²

2010

Neuroimmunomodulation

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Background: Stress influences immune function through mechanisms including an impact on regulatory elements. We have previously demonstrated that glucocorticoids (GCs) and catecholamines can influence immunomodulation including changes in Th1/Th2 cytokine production. These immunoregulatory imbalances are associated with elevated cortisol in vivo and in the presence of GCs in vitro. Methods: We examined the effects of dexamethasone (DEX) and epinephrine (EPI) on the balance of regulatory T cells (Tregs), Th1/Th2 cytokine gene expression by peripheral blood mononuclear cells (PBMCs) from 16 normal subjects after 24-hour and 11-day cultures with tetanus toxoid. We wished to determine whether the immunomodulatory effects of stress hormones involved differences in costimulatory signal pathways including CD28, CTLA-4 (CD152), and CD80/86. Results: Our results revealed that FoxP3 mRNA expression (representing Tregs) was decreased in PBMCs cultured with DEX relative to the control within 24 h (short term). DEX decreased the Th1/Th2 cytokine mRNA balance after 11 days (long term). CD28 and CD80 mRNA were decreased in short-term incubation with DEX whereas the effect of inhibition by DEX on CTLA-4 mRNA was detected only in long-term cultures. Conclusions: These results suggest that the Treg (FoxP3 mRNA) and CD28/CD80 costimulatory signal pathway may be a target of stress hormones in acute stress while the CTLA-4/CD80–86 pathway may be more susceptible in chronic stress.

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Section: Discussionsupporting

confidence: 72%

Immunomodulatory Effects of in vitroStress Hormones on FoxP3, Th1/Th2 Cytokine and Costimulatory Molecule mRNA Expression in Human Peripheral Blood Mononuclear Cells

Xiang¹,

Marshall²

2010

Neuroimmunomodulation

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“…The inhibitory effect of IL-10 plays a key role in inducing anergy, and hence has great importance in allergen-SIT [18]. The presence of peripheral blood T cells that produce IL-10 in response to allergen stimulation after immunotherapy has emerged as a consistent finding from studies of venom immunotherapy [19,20].…”

Section: Discussionmentioning

confidence: 99%

“…Treg cells are able to inhibit the development of allergic Th2 cell responses, as well as effector Th1 cell responses, and therefore play an important role in allergen-specific immunotherapy [7]. The suppressive activity of Treg cells is related to their ability to inhibit IL-2 production and to promote cell cycle arrest in CD4 + and CD8 + T cells via mechanisms that probably require cell-to-cell contact and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4)-mediated signals.…”

Section: Introductionmentioning

confidence: 99%

Induction of CD4+CD25+Foxp3+IL-10+ T Cells in HDM-Allergic Asthmatic Children with or without SIT

Wang¹,

Liu²,

Wang³

et al. 2010

Int Arch Allergy Immunol

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Background: Regulatory T cells and immunosuppressive cytokines, such as IL-10 and TGF-β₁, may have a role in clinically effective allergen-specific immunotherapy. IL-10-secreting regulatory T cells have emerged as potential mediators of immune tolerance in numerous murine models of immunopathology. The aim of this study was to evaluate the frequency and function of regulatory T cells in the response to house dust mite (HDM) immunotherapy. Methods: PBMCs were isolated from 27 HDM-allergic asthmatic children who underwent immunotherapy for 1.5–2 years (SIT group) and from 27 matched treated asthmatic children allergic to HDM (asthma group). After 48 h of in vitro stimulation with HDM extracts, regulatory T cells were measured by flow cytometry. Production of IL-4, IFN-γ and TGF-β₁in supernatants from allergen-stimulated cultures and the PBMC proliferations were measured by ELISA. Sera were tested for allergen-specific IgE using the ImmunoCAP 100 assay. Results: Patients undergoing immunotherapy produced significantly more IL-10 and showed a significant reduction in proliferation induced by HDM extract compared with the asthma group. In cultures stimulated with HDM extract, the amounts of IL-4 and TGF-β were lower and the amounts of IFN-γ were higher in the SIT group compared with the asthma group. Conclusion: There is a functional, but quantitative, insufficiency of Treg cells in allergic asthmatic children, which was reversed in SIT-treated children. SIT can up-regulate the function of CD4⁺CD25⁺Foxp3⁺ Treg cells.

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“…This is achieved through multiple mechanisms that overcome and suppress allergic inflammation [1,2,3]. One such mechanism is the regulation by allergen-specific Treg cells via the production of immunosuppressive cytokines, such as interleukin (IL)-10 and transforming growth factor-β, under various tolerogenic conditions [1,2,3]. …”

Section: Introductionmentioning

confidence: 99%

Upregulation of Interleukin-35 Subunits in Regulatory T Cells in a Murine Model of Allergic Rhinitis

Shen

Fan²,

Liu³

et al. 2014

ORL

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Objective: Regulatory T (Treg) cells play a critical role in the pathophysiology of allergic rhinitis (AR). We investigated the regulatory roles of interleukin (IL)-35, an immunosuppressive cytokine expressed by CD4⁺CD25⁺Foxp3⁺ Treg cells, in a murine model of AR. Methods: The expression of IL-35 subunits (Ebi3, encoded by Ebi3, and IL-12p35, encoded by IL12a) and IL-35 receptor chains (IL12rb and IL6st) in nasal mucosa and in spleen-derived Treg cells from ovalbumin (OVA)-sensitized AR was analyzed by immunohistochemistry and quantitative real-time RT-PCR techniques. Results: IL-35 subunit secretion was associated with local OVA sensitization in this murine model of AR. Ebi3 and IL-12p35, as well as CD3, were expressed differentially in the same regions of nasal mucosa of both AR and control animals. Ebi3 mRNA levels were significantly downregulated in the nasal mucosa of AR mice compared with control mice. Similarly, Ebi3 and IL12a mRNA levels were significantly upregulated in CD4⁺CD25⁺ Treg cells and, correspondingly, downregulated in CD4⁺CD25^- T effector (Teff) cells. IL6st mRNA levels were also significantly downregulated in CD4⁺CD25^- Teff cells. Conclusions: Decreased Ebi3 may have a crucial regulatory effect on the nasal mucosa in AR. The increased IL-35 subunit expression in CD4⁺CD25⁺ Treg cells may contribute to regulating the pathogenesis of AR. i 2014 S. Karger AG, Basel

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T-Cell Regulatory Mechanisms in Specific Immunotherapy

Cited by 45 publications

References 189 publications

Immunomodulatory Effects of in vitroStress Hormones on FoxP3, Th1/Th2 Cytokine and Costimulatory Molecule mRNA Expression in Human Peripheral Blood Mononuclear Cells

Immunomodulatory Effects of in vitroStress Hormones on FoxP3, Th1/Th2 Cytokine and Costimulatory Molecule mRNA Expression in Human Peripheral Blood Mononuclear Cells

Induction of CD4<sup>+</sup>CD25<sup>+</sup>Foxp3<sup>+</sup>IL-10<sup>+</sup> T Cells in HDM-Allergic Asthmatic Children with or without SIT

Upregulation of Interleukin-35 Subunits in Regulatory T Cells in a Murine Model of Allergic Rhinitis

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