Suppression of allergic airway inflammation in a mouse model by Der p2 recombined BCG.
Allergic asthma is a chronic inflammatory disease mediated by T helper (Th)2 cell immune responses. Currently, immunotherapies based on both immune deviation and immune suppression, including the development of recombinant mycobacteria as immunoregulatory vaccines, are attractive treatment strategies for asthma. In our previous studies, we created a genetically recombinant form of bacille Calmette-Guerin (rBCG) that expressed Der p2 of house dust mites and established that it induced a shift from a Th2 response to a Th1 response in naive mice. However, it is unclear whether rBCG could suppress allergic airway inflammation in a mouse model. In this article we report that rBCG dramatically inhibited airway inflammation, eosinophilia, mucus production and mast cell degranulation in allergic mice. Analysis of interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels in bronchoalveolar lavage fluid (BALF) and lung tissue revealed that the suppression was associated with a shift from a Th2 response to a Th1 response. At the same time, rBCG induced a CD4(+) CD25(+) Foxp3(+) T-cell subtype that could suppress the proliferation of Th2 effector cells in vitro in an antigen-specific manner. Moreover, suppression of CD4(+) CD25(+) T cells could be adoptively transferred. Thus, our results demonstrate that rBCG induces both generic and specific immune responses. The generic immune response is associated with a shift from a Th2 to a Th1 cytokine response, whereas the specific immune response against Der p2 appears to be related to the expansion of transforming growth factor-beta (TGF-beta)-producing CD4(+) CD25(+) Foxp3(+) regulatory T cells. rBCG can suppress asthmatic airway inflammation through both immune deviation and immune suppression and may be a feasible, efficient immunotherapy for asthma.
Ou-Yang
Hai-Feng
HF
Department of Respiratory Medicine, Xijing Hospital, Fourth Military Medical University, Xi'an, China.
Hu
Xing-Bin
XB
Ti
Xin-Yu
XY
Shi
Jie-Ran
JR
Li
Shu-Jun
SJ
Qi
Hao-Wen
HW
Wu
Chang-Gui
CG
D019264:Adoptive Transfer; D000818:Animals; D039741:Antigens, Dermatophagoides / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D060829:Arthropod Proteins; D001249:Asthma / Q000276:immunology / Q000628:therapy*; D001500:BCG Vaccine / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D016207:Cytokines / Q000276:immunology / Q000378:metabolism; D004195:Disease Models, Animal; D004802:Eosinophilia / Q000188:drug therapy / Q000276:immunology; D005260:Female; D016233:Immunotherapy, Active; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D015847:Interleukin-4 / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000276:immunology / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D039981:Pyroglyphidae / Q000276:immunology*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D018417:Th1 Cells / Q000276:immunology / Q000378:metabolism; D018418:Th2 Cells / Q000276:immunology / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000276:immunology / Q000378:metabolism
D039741:Antigens, Dermatophagoides; D060829:Arthropod Proteins; D001500:BCG Vaccine; D016207:Cytokines; C451163:Dermatophagoides pteronyssinus antigen p 2; D011993:Recombinant Fusion Proteins; D016212:Transforming Growth Factor beta; D015847:Interleukin-4; D007371:Interferon-gamma