scholarly journals Peripheral blood basophils are the main source for early interleukin-4 secretion upon in vitro stimulation with Culicoides allergen in allergic horses

PLoS ONE ◽  
2021 ◽  
Vol 16 (5) ◽  
pp. e0252243
Author(s):  
Fahad Raza ◽  
Susanna Babasyan ◽  
Elisabeth M. Larson ◽  
Heather S. Freer ◽  
Christiane L. Schnabel ◽  
...  

Interleukin-4 (IL-4) is a key cytokine secreted by type 2 T helper (Th2) cells that orchestrates immune responses during allergic reactions. Human and mouse studies additionally suggest that basophils have a unique role in the regulation of allergic diseases by providing initial IL-4 to drive T cell development towards the Th2 phenotype. Equine Culicoides hypersensitivity (CH) is a seasonal immunoglobulin E (IgE)-mediated allergic dermatitis in horses in response to salivary allergens from Culicoides (Cul) midges. Here, we analyzed IL-4 production in peripheral blood mononuclear cells (PBMC) of CH affected (n = 8) and healthy horses (n = 8) living together in an environment with natural Cul exposure. During Cul exposure when allergic horses had clinical allergy, IL-4 secretion from PBMC after stimulation with Cul extract was similar between healthy and CH affected horses. In contrast, allergic horses had higher IL-4 secretion from PBMC than healthy horses during months without allergen exposure. In addition, allergic horses had increased percentages of IL-4+ cells after Cul stimulation compared to healthy horses, while both groups had similar percentages of IL-4+ cells following IgE crosslinking. The IL-4+ cells were subsequently characterized using different cell surface markers as basophils, while very few allergen-specific CD4+ cells were detected in PBMC after Cul extract stimulation. Similarly, IgE crosslinking by anti-IgE triggered basophils to produce IL-4 in all horses. PMA/ionomycin consistently induced high percentages of IL-4+ Th2 cells in both groups confirming that T cells of all horses studied were capable of IL-4 production. In conclusion, peripheral blood basophils produced high amounts of IL-4 in allergic horses after stimulation with Cul allergens, and allergic horses also maintained higher basophil percentages throughout the year than healthy horses. These new findings suggest that peripheral blood basophils may play a yet underestimated role in innate IL-4 production upon allergen activation in horses with CH. Basophil-derived IL-4 might be a crucial early signal for immune induction, modulating of immune responses towards Th2 immunity and IgE production.

2001 ◽  
Vol 69 (2) ◽  
pp. 665-672 ◽  
Author(s):  
Claudia I. Brodskyn ◽  
Gregory K. DeKrey ◽  
Richard G. Titus

ABSTRACT The importance of CD40, CD80, and CD86 costimulatory molecules in anti-Leishmania immune responses has been established in murine models. A role for these costimulatory molecules in human anti-Leishmania immune responses was investigated in this study. Autologous macrophages and peripheral blood leukocytes (PBL) were prepared from peripheral blood mononuclear cells ofLeishmania-naive donors and cultured with or withoutLeishmania major in various combinations. After 7 days of culture, high levels of CD40 and CD86 were expressed on macrophages in the presence or absence of L. major. When macrophages were cultured for an additional 7 days with PBL, expression of all three costimulatory molecules was detected. When L. major was present in these cultures, the expression of CD80, and to a lesser extent CD40, on macrophages was enhanced. Blockade of CD80, CD86, or both molecules (in the order of greatest effect) in cultures containing macrophages, PBL, and L. major significantly inhibited the production of gamma interferon, interleukin-5 (IL-5), and IL-12. Blockade of CD40-CD154 interactions also significantly inhibited production of these cytokines in response to L. major. Production of IL-10 was unaltered by the blockade of these costimulatory molecules. Thus, these data suggest that CD40, CD80, and CD86 expression and regulation may significantly impact anti-Leishmania immune responses in humans.


2018 ◽  
Vol 68 (2) ◽  
pp. 201-210
Author(s):  
Hiromichi Ohtsuka ◽  
Maki Inoue ◽  
Yosuke Maeda ◽  
Taishi Tanabe ◽  
Motoshi Tajima

Abstract The expressions of cytokines mRNA, including interleukin-4 (IL-4), interleukin- 17A (IL-17A) and interferon-gamma (IFN-γ), their master regulatory transcription factors, and signal transducers and activator of transcription (STAT) stimulated in vitro with Pasteurella (P.) multocida soluble antigen were examined in peripheral blood mononuclear cells (PBMC) from Holstein calves. The healthy Holstein calves were divided into three groups; 2 weeks old (2W Group, N=8), 6 weeks old (6W Group, N=8), and 10 weeks old (10W Group, N=8). PBMC were stimulated in vitro by soluble antigen of P. multocida. There were significantly lower expressions of IFN-γ, IL-4, and STAT-6 mRNA of PBMC stimulated with P. multocida soluble antigen in the 2W Group compared to that in the 10W Group. Expression of IL-17A and IFN-γ in PBMC stimulated with P. multocida soluble antigen were significantly higher compared with the PBMC without stimulation in the 6W groups. The results of the present study demonstrated that 2W old calves had decreased cytokine expression of PBMC when in vitro stimulated with P. multocida soluble antigen in vitro.


2011 ◽  
Vol 2011 ◽  
pp. 1-6 ◽  
Author(s):  
Reetta Holma ◽  
Riina A. Kekkonen ◽  
Katja Hatakka ◽  
Tuija Poussa ◽  
Outi Vaarala ◽  
...  

Probiotics and prebiotics modify the intestinal environment and could have immunomodulatory effects. The proliferation of spontaneous and phytohemagglutinin-stimulated peripheral blood mononuclear cells (PBMCs) and their production of interleukin-4, interleukin-5, transforming growth factor-β1, and interferon-γ (IFNγ) were determined in eighteen men at the baseline and during a 2-week period of probiotics (mixture of Lactobacillus rhamnosus GG, Lactobacillus rhamnosus LC705, Propionibacterium freudenreichii ssp. shermanii JS, and Bifidobacterium breve Bb99) and galactooligosaccharides (GOSs) (3.8 g/day). The spontaneous and stimulated proliferation of PBMC increased from the baseline during probiotics+GOS (P<0.001). The secretion of IFNγ, but not other cytokines, by stimulated PBMC increased during the same period (P<0.05). In conclusion, the consumption of this probiotic mixture including GOS appears to increase the capacity of PBMC to proliferate and release IFNγ selectively in healthy men.


2022 ◽  
Vol 12 ◽  
Author(s):  
Simone Negrini ◽  
Paola Contini ◽  
Giuseppe Murdaca ◽  
Francesco Puppo

Allergy is an inflammatory process determined by a cascade of immune events characterized by T-helper 2 lymphocytes polarization leading to interleukin-4 upregulation, IgE secretion, and mast cell and eosinophil activation. HLA-G molecules, both in membrane-bound and in soluble forms, are known to play a key immunoregulatory role and their involvement in allergic diseases is supported by increasing literature data. HLA-G expression and secretion is specifically induced in peripheral blood mononuclear cells of allergic patients after in vitro incubation with the causal allergen. Elevated levels of soluble HLA-G molecules are detected in serum of patients with allergic rhinitis correlating with allergen-specific IgE levels, clinical severity, drug consumption and response to allergen-specific immunotherapy. HLA-G genetic polymorphisms confer susceptibility to allergic asthma development and high levels of soluble HLA-G molecules are found in plasma and bronchoalveolar lavage fluid of patients with allergic asthma correlating with allergen-specific IgE levels. Interestingly, allergic pregnant women have lower plasma sHLA-G levels than non-allergic women during the 3rd trimester of pregnancy and at delivery. Finally, in allergic patients with atopic dermatitis HLA-G molecules are expressed by T cells, monocytes-macrophages and Langerhans cells infiltrating the dermis. Although at present is difficult to completely define the role of HLA-G molecules in allergic diseases, it may be suggested that they are specifically expressed and secreted by immune cells during the allergic reaction in an attempt to suppress allergic inflammation.


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