T cell epitopes of Per a 10 modulate local-systemic immune responses and airway inflammation by augmenting Th1 and T regulatory cell functions in murine model

•Evaluation of immunotherapeutic potential of Per a 10 derived T cell peptides.•Peptide treatment rescues lung inflammation and regulates memory B cell responses.•Local and systemic regulation of immune responses leads to tolerance generation.•T-P8 and T-P10 suppress Th2 cytokine milieu and modulate...

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Bibliographic Details
Published in:Immunobiology (1979) 2019-05, Vol.224 (3), p.462-469
Main Authors: Govindaraj, Dhanapal, Sharma, Swati, Singh, Naresh, Arora, Naveen
Format: Article
Language:English
Subjects:
Airway inflammation
Allergens - immunology
Animals
Asthma - immunology
Asthma - therapy
Disease Models, Animal
Epitopes, T-Lymphocyte - immunology
Female
Forkhead Transcription Factors - metabolism
Humans
Immune deviation
Immunity, Cellular
Immunoglobulin E - metabolism
Immunomodulation
Immunotherapy
Immunotherapy - methods
Insect Proteins - immunology
Mice
Mice, Inbred BALB C
Respiratory Hypersensitivity - immunology
Respiratory Hypersensitivity - therapy
T cell
T-Lymphocytes, Regulatory - immunology
Th1 Cells - immunology
Th2 response
tolerance
Vaccines, Subunit
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Summary:•Evaluation of immunotherapeutic potential of Per a 10 derived T cell peptides.•Peptide treatment rescues lung inflammation and regulates memory B cell responses.•Local and systemic regulation of immune responses leads to tolerance generation.•T-P8 and T-P10 suppress Th2 cytokine milieu and modulate Th1 and Treg effector functions.•Peptides T-P8 and T-P10 demonstrated efficacy in murine model of airway disease. Peptide immunotherapy (PIT) represents a safe and efficacious therapeutic modality for allergic diseases. Present study evaluates immunotherapeutic potential of T cell peptides of major cockroach allergen, Per a 10 in murine model of airway allergy. Treatment with peptides T-P8 and T-P10 demonstrated maximal resolution of pathophysiological features such as reduced recruitment of inflammatory cells to airways, lowered specific IgE, induction of IgG2a antibodies in serum, immune deviation towards Th1 cytokine milieu, suppression of Th2 cytokines in BALF and splenocyte culture supernatant and resolution of lung inflammation. A significant increase in CD4+Foxp3+ cells in spleen indicate towards induction of T regulatory cell mediated peripheral tolerance characterized by shift in cytokine milieu from Th2 to T regulatory cytokines. PIT modulates regulation of immune responses at both local and systemic levels, contributes towards holistic improvement in allergic features in mice and thus demonstrate potential for safe, specific and efficacious treatment for cockroach allergy.
ISSN:0171-2985
1878-3279
DOI:10.1016/j.imbio.2019.01.003