In vitro induction of functional allergen‐specific <scp>CD</scp>4+ <scp>CD</scp>25high Treg cells in horses affected with insect bite hypersensitivity

Hamza, Eman; Akdiş, Cezmi A.; Wagner, Bettina; Steinbach, Falko; Marti, Eliane

doi:10.1111/cea.12131

Cited by 27 publications

(24 citation statements)

References 37 publications

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“…According to our studies on the immune response and pathogenesis of IBH, Icelandic horses exported from Iceland to Europe develop a stronger Th2 polarized immune response than their disease status matched counterparts born in Switzerland (Hamza et al, 2007). Further studies demonstrated an imbalance between the Th2/Treg immune response in IBH, using both Culicoides stimulated PBMC and skin biopsies (Hamza et al, 2008;Hamza et al, 2013;Heimann et al, 2011). These findings indicate that a preventive immunization against IBH should aim at inducing an allergen-specific Treg and/or Th1 immune response.…”

Section: Introductionmentioning

confidence: 74%

A preventive immunization approach against insect bite hypersensitivity: Intralymphatic injection with recombinant allergens in Alum or Alum and monophosphoryl lipid A

Jónsdóttir

Svansson

Stefánsdóttir

et al. 2016

Veterinary Immunology and Immunopathology

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Insect bite hypersensitivity (IBH) is an IgE-mediated dermatitis of horses caused by bites of Culicoides insects, not indigenous to Iceland. Horses born in Iceland and exported to Culicoides-rich areas are frequently affected with IBH. The aims of the study were to compare immunization with recombinant allergens using the adjuvant aluminum hydroxide (Alum) alone or combined with monophosphoryl lipid A (MPLA) for development of a preventive immunization against IBH. Twelve healthy Icelandic horses were vaccinated intralymphatically three times with 10 μg each of four recombinant Culicoides nubeculosus allergens in Alum or in Alum/MPLA. Injection with allergens in both Alum and Alum/MPLA resulted in significant increase in specific IgG subclasses and IgA against all r-allergens with no significant differences between the adjuvant groups. The induced antibodies from both groups could block binding of allergen specific IgE from IBH affected horses to a similar extent. No IgE-mediated reactions were induced. Allergen-stimulated PBMC from Alum/MPLA horses but not from Alum only horses produced significantly more IFNγ and IL-10 than PBMC from non-vaccinated control horses. In conclusion, intralymphatic administration of small amounts of pure allergens in Alum/MPLA induces high IgG antibody levels and Th1/Treg immune response and is a promising approach for immunoprophylaxis and immunotherapy against IBH.

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Section: Introductionmentioning

confidence: 74%

A preventive immunization approach against insect bite hypersensitivity: Intralymphatic injection with recombinant allergens in Alum or Alum and monophosphoryl lipid A

Jónsdóttir

Svansson

Stefánsdóttir

et al. 2016

Veterinary Immunology and Immunopathology

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“…Current definitions of RAO and IAD are based on cytologic variable, and the relationship between hypersensitivity and cytology is still unclear . Some studies have reported AH predominantly in mast cell‐type or eosinophilic IAD, which might fit with the atopic, Th2‐primed immune response observed in IBH, but a recent report did not confirm these associations …”

Section: Discussionmentioning

confidence: 99%

Insect Bite Hypersensitivity in Horses is Associated with Airway Hyperreactivity

Lanz

Brunner

Graubner

et al. 2017

Veterinary Internal Medicne

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BackgroundGenetic and epidemiologic evidence suggests that in horses, as in other species, different manifestations of hypersensitivity may occur together.HypothesisHorses affected with insect bite hypersensitivity (IBH) show airway hyperreactivity (AH) to inhaled histamine, even in the absence of overt clinical signs of equine asthma (EA).AnimalsTwenty‐two healthy controls (group C), 24 horses suffering from IBH alone (group IBH), and 23 horses suffering from IBH and EA (group IBH/EA).MethodsThe clinical histories were assessed using 2 standardized questionnaires, the Horse Owner Assessed Respiratory Signs Index (HOARSI), and IBH scoring. Horses were classified as EA‐affected if their HOARSI was >1 and as IBH‐affected if IBH score was >0. Confounding disorders were excluded by clinical examination. The arterial partial pressure of oxygen (PaO2) was measured and flowmetric plethysmography used to assess airway reactivity to increasing doses of inhaled histamine.ResultsThe median histamine provocation concentration (PC) when ∆flow values increased by 35% (PC35) was significantly higher in group C (5.94 [1.11–26.33] mg/mL) compared to group IBH (2.95 [0.23–10.13] mg/mL) and group IBH/EA (2.03 [0.43–10.94] mg/mL; P < 0.01). The PC50 and PC75 showed very similar differences between groups. Furthermore, PaO2 was significantly lower in group IBH (84 ± 8 mmHg) and group IBH/EA (78 ± 11 mmHg) compared to group C (89 ± 6 mmHg; P < 0.01).Conclusions and Clinical Importance IBH is associated with AH and decreased PaO2, even in the absence of overt respiratory clinical signs.

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“…Nevertheless, researchers should be encouraged by the progress made so far in identifying and expressing allergens from the most relevant Culicoides spp. and the recent demonstration that Culicoides salivary antigens can be used to induce T-regs in an in vitro model of equine IBH (122).…”

Section: Immunotherapymentioning

confidence: 99%

“…Conversely, the addition of neutralizing antibodies to IL10 and TGFbeta to antigen stimulated cultures of PBL from healthy horses caused an elevation in the numbers of IL4 producing T cells (120). Subsequently, higher numbers of FoxP3 CD4+ CD25+ cells were detected in Culicoides antigen stimulated PBL from healthy horses compared to cultures of cells from horses with IBH (121), and induced CD4+ CD25 hi T cells from healthy showed increased suppression of CD4+ T-cell responses to Culicoides antigens (122) Together, these results show that the key difference between healthy and IBH-affected horses is the presence of regulatory T cells, which act to limit the nascent Thelper 2 response stimulated by Culicoides saliva.…”

Section: Cellular Immune Responses In Ibhmentioning

confidence: 99%

Immune responses to ectoparasites of horses, with a focus on insect bite hypersensitivity

Wilson

2014

Parasite Immunology

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Horses are affected by a wide variety of arthropod ectoparasites, ranging from lice which spend their entire life on the host, through ticks which feed over a period of days, to numerous biting insects that only transiently visit the host to feed. The presence of ectoparasites elicits a number of host responses including innate inflammatory responses, adaptive immune reactions and altered behaviour; all of which can reduce the severity of the parasite burden. All of these different responses are linked through immune mechanisms mediated by mast cells and IgE antibodies which have an important role in host resistance to ectoparasites, yet immune responses also cause severe pathological reactions. One of the best described examples of such pathological sequelae is insect bite hypersensitivity (IBH) of horses; an IgE-mediated type 1 hypersensitivity to the salivary proteins of Culicoides spp. associated with T-helper-2 production of IL4 and IL13. Importantly, all horses exposed to Culicoides have an expanded population of Culicoides antigen-specific T cells with this pattern of cytokine production, but in those which remain healthy, the inflammatory reaction is tempered by the presence of FoxP3+ CD4+ regulatory T cells that express IL10 and TGF-beta, which suppresses the IL4 production by Culicoides antigen-activated T cells.

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In vitro induction of functional allergen‐specific CD4⁺ CD25^high Treg cells in horses affected with insect bite hypersensitivity

Abstract: The in vitro induction of functional allergen-specific Treg cells in IBH-affected horses suggests a potential therapeutic use of these cells in allergy.

Cited by 27 publications

References 37 publications

A preventive immunization approach against insect bite hypersensitivity: Intralymphatic injection with recombinant allergens in Alum or Alum and monophosphoryl lipid A

A preventive immunization approach against insect bite hypersensitivity: Intralymphatic injection with recombinant allergens in Alum or Alum and monophosphoryl lipid A

Insect Bite Hypersensitivity in Horses is Associated with Airway Hyperreactivity

Immune responses to ectoparasites of horses, with a focus on insect bite hypersensitivity

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In vitro induction of functional allergen‐specific CD4+ CD25high Treg cells in horses affected with insect bite hypersensitivity

Abstract: The in vitro induction of functional allergen-specific Treg cells in IBH-affected horses suggests a potential therapeutic use of these cells in allergy.

Cited by 27 publications

References 37 publications

A preventive immunization approach against insect bite hypersensitivity: Intralymphatic injection with recombinant allergens in Alum or Alum and monophosphoryl lipid A

A preventive immunization approach against insect bite hypersensitivity: Intralymphatic injection with recombinant allergens in Alum or Alum and monophosphoryl lipid A

Insect Bite Hypersensitivity in Horses is Associated with Airway Hyperreactivity

Immune responses to ectoparasites of horses, with a focus on insect bite hypersensitivity

Contact Info

Product

Resources

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In vitro induction of functional allergen‐specific CD4⁺ CD25^high Treg cells in horses affected with insect bite hypersensitivity