Neonatal bacillus Calmette-Guérin vaccination inhibits de novo allergic inflammatory response in mice via alteration of CD4+CD25+ T-regulatory cells.
OBJECTIVE
The hygiene hypothesis suggests a lack of bacterial infections would favor the development of allergic diseases. Mycobacterium bovis bacille Calmette-Guérin (BCG) infection can inhibit allergen-induced asthma reactions, but the underlying mechanism of this infection on the immunological responses is unclear. T-regulatory (Treg) cells are thought to play a role as a crucial immunoregulatory cells that are capable of regulating adaptive immune responses. We conducted this study to investigate whether the protective effect of the BCG vaccination on allergic pulmonary inflammation is associated with the alteration of CD4+CD25+ Treg cells in a murine asthma model and the mechanisms of Treg cells.


METHODS
Newborn C57BL/6 mice were vaccinated 3 times with BCG on d 0, 7, and 14 and subsequently sensitized and challenged with ovalbumin. Eosinophil infiltration was investigated. The frequencies of spleen CD4+CD25+ Treg cells and the expression of specific transcriptional factor Foxp3 were assayed. The cytotoxic lymphocyte associated antigen (CTLA)-4 expression and cytokine interleukin-10 (IL-10) and transforming growth factor-beta (TGF-beta) levels were measured.


RESULTS
We showed that treatment of mice with BCG inhibited de novo allergic inflammatory response in a mouse model of asthma. BCG treatments are associated with the increase of CD4+CD25+ Treg cells and Foxp3 expression, accompanied by an increased CTLA-4 expression and cytokine IL-10 and TGF-beta levels (P<0.05).


CONCLUSIONS
Neonatal BCG vaccinations ameliorate de novo local eosinophilic inflammation induced by allergen and increase the numbers of CD4+CD25+ Treg cells and Foxp3 expression. The cell-cell contact inhibition and regulatory cytokine production may be involved in the regulatory mechanism.
Li
Qian
Q
Department of Respiratory Medicine, Second Affiliated Hospital, Zhejiang University College of Medicine, Hangzhou 310009, China.
Shen
Hua-hao
HH
D000818:Animals; D000831:Animals, Newborn / Q000276:immunology*; D001500:BCG Vaccine / Q000276:immunology*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D015704:CD4 Antigens / Q000276:immunology*; D002478:Cells, Cultured; D004804:Eosinophils / Q000166:cytology / Q000276:immunology; D051858:Forkhead Transcription Factors / Q000378:metabolism; D006801:Humans; D006967:Hypersensitivity / Q000276:immunology*; D007249:Inflammation / Q000276:immunology* / Q000517:prevention & control; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology*; D008168:Lung / Q000166:cytology / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D013154:Spleen / Q000166:cytology / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology*
D001500:BCG Vaccine; D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit