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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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FCM detection of PD-1 and CTLA-4 on the surface of CD4+CD25+Foxp3+Treg cells in peripheral blood, mediastinal draining lymph nodes, and spleen of mice. To evaluate whether Treg cells in this study could play their role by contact inhibition, the surface expression of two major negative co-stimulatory molecules were detected by FCM. Freshly isolated cells from blood, mediastinal draining lymph nodes and spleen were stained with fluorescently antibodies for CD4, CD25, Foxp3 and PD-1 or CTLA-4. The results showed a significantly higher levels of PD-1 and CTLA-4 on the surface of Treg cells in MAPs treated mice than in control mice and OVA treated mice (gating on CD4+CD25+ cells).
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Figure 6: FCM detection of PD-1 and CTLA-4 on the surface of CD4+CD25+Foxp3+Treg cells in peripheral blood, mediastinal draining lymph nodes, and spleen of mice. To evaluate whether Treg cells in this study could play their role by contact inhibition, the surface expression of two major negative co-stimulatory molecules were detected by FCM. Freshly isolated cells from blood, mediastinal draining lymph nodes and spleen were stained with fluorescently antibodies for CD4, CD25, Foxp3 and PD-1 or CTLA-4. The results showed a significantly higher levels of PD-1 and CTLA-4 on the surface of Treg cells in MAPs treated mice than in control mice and OVA treated mice (gating on CD4+CD25+ cells).

Mentions: Cell-cell contacting is the other mechanism of Treg function, co-stimulatory molecules such as programmed death (PD)-1 and cytotoxic T lymphocyte associated antigen (CTLA)-4 contribute to the regulatory function of Treg cells. Therefore, we investigated the expression of PD-1 and CTLA-4 on the surface of Treg cells by FCM. Interestingly, compared to the control mice, OVA challenge elevated the expression of PD-1 mildly, however, the ratio of PD-1+ Treg cells increased significantly after treatment with OVA323-339MAP in blood, mediastinal draining lymph nodes, and spleen. The similar alteration of CTLA-4 expression on the surface of Treg cells was observed in same tissues (Figure 6).


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 PD-1 and CTLA-4 on the surface of CD4+CD25+Foxp3+Treg cells in peripheral blood, mediastinal draining lymph nodes, and spleen of mice. To evaluate whether Treg cells in this study could play their role by contact inhibition, the surface expression of two major negative co-stimulatory molecules were detected by FCM. Freshly isolated cells from blood, mediastinal draining lymph nodes and spleen were stained with fluorescently antibodies for CD4, CD25, Foxp3 and PD-1 or CTLA-4. The results showed a significantly higher levels of PD-1 and CTLA-4 on the surface of Treg cells in MAPs treated mice than in control mice and OVA treated mice (gating on CD4+CD25+ cells).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 6: FCM detection of PD-1 and CTLA-4 on the surface of CD4+CD25+Foxp3+Treg cells in peripheral blood, mediastinal draining lymph nodes, and spleen of mice. To evaluate whether Treg cells in this study could play their role by contact inhibition, the surface expression of two major negative co-stimulatory molecules were detected by FCM. Freshly isolated cells from blood, mediastinal draining lymph nodes and spleen were stained with fluorescently antibodies for CD4, CD25, Foxp3 and PD-1 or CTLA-4. The results showed a significantly higher levels of PD-1 and CTLA-4 on the surface of Treg cells in MAPs treated mice than in control mice and OVA treated mice (gating on CD4+CD25+ cells).
Mentions: Cell-cell contacting is the other mechanism of Treg function, co-stimulatory molecules such as programmed death (PD)-1 and cytotoxic T lymphocyte associated antigen (CTLA)-4 contribute to the regulatory function of Treg cells. Therefore, we investigated the expression of PD-1 and CTLA-4 on the surface of Treg cells by FCM. Interestingly, compared to the control mice, OVA challenge elevated the expression of PD-1 mildly, however, the ratio of PD-1+ Treg cells increased significantly after treatment with OVA323-339MAP in blood, mediastinal draining lymph nodes, and spleen. The similar alteration of CTLA-4 expression on the surface of Treg cells was observed in same tissues (Figure 6).

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