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Synthesized OVA323-339MAP octamers mitigate OVA-induced airway inflammation by regulating Foxp3 T regulatory cells.

Su W, Zhong W, Zhang Y, Xia Z - BMC Immunol. (2012)

Bottom Line: These results were further correlated with the decreased OVA specific immunoglobulin E (sIgE) level and the infiltration of inflammatory cells such as eosinophils and lymphocytes in BALF.However, OVA323-339 peptide monomers did not show any of the mentioned effects in the same animal model.Our study indicates that OVA323-339MAP had significant therapeutic effects on mice allergic airway inflammation by regulating the balance of Th1/Th2 response through Treg cells in vivo.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

ABSTRACT

Background: Antigen-specific immunotherapy (SIT) has been widely practiced in treating allergic diseases such as asthma. However, this therapy may induce a series of allergic adverse events during treatment. Peptide immunotherapy (PIT) was explored to overcome these disadvantages. We confirmed that multiple antigen peptides (MAPs) do not cause autoimmune responses, which led to the presumption that MAPs intervention could alleviate allergic airway inflammation without inducing adverse effects.

Results: In this study, synthesized OVA323-339MAP octamers were subcutaneously injected into ovalbumin (OVA)-sensitized and -challenged Balb/c mice to observe its effect on allergic airway inflammation, Th2 immune response, and immune regulating function. It was confirmed that OVA sensitization and challenge led to significant peritracheal inflammatory, cell infiltration, and intensive Th2 response. Treatment of OVA323-339MAP octomers in the airway inflammation mice model increased CD4+CD25+Foxp3+ T regulatory (Treg) cells and their regulatory function in peripheral blood, mediastinal draining lymph nodes, and the spleen. Furthermore, OVA323-339MAP increased IL-10 levels in bronchial alveolar lavage fluid (BALF); up-regulated the expression of IL-10, membrane-bound TGF-β1, as well as Foxp3 in lung tissues; and up-regulated programmed death-1 (PD-1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4) on the surface of Treg cells. These results were further correlated with the decreased OVA specific immunoglobulin E (sIgE) level and the infiltration of inflammatory cells such as eosinophils and lymphocytes in BALF. However, OVA323-339 peptide monomers did not show any of the mentioned effects in the same animal model.

Conclusions: Our study indicates that OVA323-339MAP had significant therapeutic effects on mice allergic airway inflammation by regulating the balance of Th1/Th2 response through Treg cells in vivo.

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Related in: MedlinePlus

FCM detection of the inhibitory effect of Treg cells on Teff proliferation. CD4+CD25+ T cells from normal mice and OVA-challenged with or without intervention mice were isolated using immunomagnetic beads, then co-cultured with effector CD4+ lymphocytes and CD11c+ APC from normal mice for 5 days with OVA (1 mg/ml) stimulation. Effector T cells proliferation in response to OVA stimulation was assessed by FCM. The results showed that the proliferation cycles of Teff cells co-cultured with OVA323-339MAP group were four cycles, less than that in the OVA group and Teff without Treg cells group (six cycles). Data represent one of three independent experiments.
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Figure 7: FCM detection of the inhibitory effect of Treg cells on Teff proliferation. CD4+CD25+ T cells from normal mice and OVA-challenged with or without intervention mice were isolated using immunomagnetic beads, then co-cultured with effector CD4+ lymphocytes and CD11c+ APC from normal mice for 5 days with OVA (1 mg/ml) stimulation. Effector T cells proliferation in response to OVA stimulation was assessed by FCM. The results showed that the proliferation cycles of Teff cells co-cultured with OVA323-339MAP group were four cycles, less than that in the OVA group and Teff without Treg cells group (six cycles). Data represent one of three independent experiments.

Mentions: To further assess the function of Treg cells in these mice, we isolated CD4+CD25+ Treg cells from OVA-challenged mice, with or without OVA323-339MAP treatment. The Treg cells were co-cultured with effector CD4+ lymphocytes and CD11c+ antigen presenting cells (APCs) from the normal untreated mice. Five days later, effector T cells proliferation in response to in vitro OVA stimulation was assessed by FCM. The results showed that effector T cells underwent six proliferation cycles when they were cultured with Treg cells from OVA-challenged mice, the same as that of effector T cells without Treg. Despite OVA challenge, the Treg cells from the mice treated with OVA323-339MAP displayed a regulatory function, as evidenced by reduced effector T cell proliferation cycles (Figure 7).


Synthesized OVA323-339MAP octamers mitigate OVA-induced airway inflammation by regulating Foxp3 T regulatory cells.

Su W, Zhong W, Zhang Y, Xia Z - BMC Immunol. (2012)

FCM detection of the inhibitory effect of Treg cells on Teff proliferation. CD4+CD25+ T cells from normal mice and OVA-challenged with or without intervention mice were isolated using immunomagnetic beads, then co-cultured with effector CD4+ lymphocytes and CD11c+ APC from normal mice for 5 days with OVA (1 mg/ml) stimulation. Effector T cells proliferation in response to OVA stimulation was assessed by FCM. The results showed that the proliferation cycles of Teff cells co-cultured with OVA323-339MAP group were four cycles, less than that in the OVA group and Teff without Treg cells group (six cycles). Data represent one of three independent experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3472185&req=5

Figure 7: FCM detection of the inhibitory effect of Treg cells on Teff proliferation. CD4+CD25+ T cells from normal mice and OVA-challenged with or without intervention mice were isolated using immunomagnetic beads, then co-cultured with effector CD4+ lymphocytes and CD11c+ APC from normal mice for 5 days with OVA (1 mg/ml) stimulation. Effector T cells proliferation in response to OVA stimulation was assessed by FCM. The results showed that the proliferation cycles of Teff cells co-cultured with OVA323-339MAP group were four cycles, less than that in the OVA group and Teff without Treg cells group (six cycles). Data represent one of three independent experiments.
Mentions: To further assess the function of Treg cells in these mice, we isolated CD4+CD25+ Treg cells from OVA-challenged mice, with or without OVA323-339MAP treatment. The Treg cells were co-cultured with effector CD4+ lymphocytes and CD11c+ antigen presenting cells (APCs) from the normal untreated mice. Five days later, effector T cells proliferation in response to in vitro OVA stimulation was assessed by FCM. The results showed that effector T cells underwent six proliferation cycles when they were cultured with Treg cells from OVA-challenged mice, the same as that of effector T cells without Treg. Despite OVA challenge, the Treg cells from the mice treated with OVA323-339MAP displayed a regulatory function, as evidenced by reduced effector T cell proliferation cycles (Figure 7).

Bottom Line: These results were further correlated with the decreased OVA specific immunoglobulin E (sIgE) level and the infiltration of inflammatory cells such as eosinophils and lymphocytes in BALF.However, OVA323-339 peptide monomers did not show any of the mentioned effects in the same animal model.Our study indicates that OVA323-339MAP had significant therapeutic effects on mice allergic airway inflammation by regulating the balance of Th1/Th2 response through Treg cells in vivo.

View Article: PubMed Central - HTML - PubMed

Affiliation: Department of Pediatrics, Ruijin Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.

ABSTRACT

Background: Antigen-specific immunotherapy (SIT) has been widely practiced in treating allergic diseases such as asthma. However, this therapy may induce a series of allergic adverse events during treatment. Peptide immunotherapy (PIT) was explored to overcome these disadvantages. We confirmed that multiple antigen peptides (MAPs) do not cause autoimmune responses, which led to the presumption that MAPs intervention could alleviate allergic airway inflammation without inducing adverse effects.

Results: In this study, synthesized OVA323-339MAP octamers were subcutaneously injected into ovalbumin (OVA)-sensitized and -challenged Balb/c mice to observe its effect on allergic airway inflammation, Th2 immune response, and immune regulating function. It was confirmed that OVA sensitization and challenge led to significant peritracheal inflammatory, cell infiltration, and intensive Th2 response. Treatment of OVA323-339MAP octomers in the airway inflammation mice model increased CD4+CD25+Foxp3+ T regulatory (Treg) cells and their regulatory function in peripheral blood, mediastinal draining lymph nodes, and the spleen. Furthermore, OVA323-339MAP increased IL-10 levels in bronchial alveolar lavage fluid (BALF); up-regulated the expression of IL-10, membrane-bound TGF-β1, as well as Foxp3 in lung tissues; and up-regulated programmed death-1 (PD-1) and cytotoxic T lymphocyte associated antigen 4 (CTLA-4) on the surface of Treg cells. These results were further correlated with the decreased OVA specific immunoglobulin E (sIgE) level and the infiltration of inflammatory cells such as eosinophils and lymphocytes in BALF. However, OVA323-339 peptide monomers did not show any of the mentioned effects in the same animal model.

Conclusions: Our study indicates that OVA323-339MAP had significant therapeutic effects on mice allergic airway inflammation by regulating the balance of Th1/Th2 response through Treg cells in vivo.

Show MeSH
Related in: MedlinePlus