Lactobacillus reuteri-induced regulatory T cells protect against an allergic airway response in mice.
BACKGROUND
We have previously demonstrated that oral treatment with live Lactobacillus reuteri can attenuate major characteristics of the asthmatic response in a mouse model of allergic airway inflammation. However, the mechanisms underlying these effects remain to be determined.


OBJECTIVE
We tested the hypothesis that regulatory T cells play a major role in mediating L. reuteri-induced attenuation of the allergic airway response.


METHODS
BALB/c mice were treated daily with L. reuteri by gavage. Flourescent-activated cell sorter analysis was used to determine CD4(+)CD25(+)Foxp3(+)T cell populations in spleens following treatment with L. reuteri or vehicle control. Cell proliferation assays were performed on immunomagnetic bead separated CD4(+)CD25(+) and CD4(+)CD25(-) T cells. CD4(+)CD25(+) T cells isolated from, ovalbumin naive, L. reuteri treated mice were transferred into ovalbumin-sensitized mice. Following antigen challenge the airway responsiveness, inflammatory cell influx and cytokine levels in bronchoalveolar lavage fluid of recipient mice were assessed.


RESULTS
Following 9 days of oral L. reuteri treatment, the percentage and total number of CD4(+)CD25(+)Foxp3(+)T cells in spleens significantly increased. CD4(+)CD25(+) cells isolated from L. reuteri-fed animals also had greater capacity to suppress T-effector cell proliferation. Adoptive transfer of CD4(+)CD25(+) T cells from L. reuteri-treated mice to ovalbumin-sensitized animals attenuated airway hyper-responsiveness and inflammation in response to subsequent antigen challenge.


CONCLUSIONS
These results strongly support a role for nonantigen-specific CD4(+)CD25(+)Foxp3(+) regulatory T cells in attenuating the allergic airway response following oral treatment with L. reuteri. This potent immuno-regulatory action may have therapeutic potential in controlling the Th2 bias observed in atopic individuals.
Karimi
Khalil
K
The Brain-Body Institute, St. Joseph's Healthcare, 50 Charlton Avenue East, T3312, Hamilton, ON L8N 4A6, Canada.
Inman
Mark D
MD
Bienenstock
John
J
Forsythe
Paul
P
D000284:Administration, Oral; D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D015704:CD4 Antigens / Q000276:immunology; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005500:Follow-Up Studies; D051858:Forkhead Transcription Factors / Q000096:biosynthesis; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D052200:Limosilactobacillus reuteri; D008168:Lung / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D019936:Probiotics / Q000008:administration & dosage / Q000627:therapeutic use*; D012130:Respiratory Hypersensitivity / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013154:Spleen / Q000276:immunology / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D016896:Treatment Outcome
D015704:CD4 Antigens; D051858:Forkhead Transcription Factors; C498833:Foxp3 protein, mouse; D053645:Interleukin-2 Receptor alpha Subunit