Lactobacillus reuteri-induced regulatory T cells protect against an allergic airway response in mice

Am J Respir Crit Care Med. 2009 Feb 1;179(3):186-93. doi: 10.1164/rccm.200806-951OC. Epub 2008 Nov 21.

Abstract

Rationale: 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.

Objectives: 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.

Measurements and main 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.

Publication types

  • Comparative Study

MeSH terms

  • Administration, Oral
  • Animals
  • Bronchoalveolar Lavage Fluid / chemistry
  • Bronchoalveolar Lavage Fluid / cytology
  • CD4 Antigens / immunology
  • Disease Models, Animal
  • Enzyme-Linked Immunosorbent Assay
  • Follow-Up Studies
  • Forkhead Transcription Factors / biosynthesis
  • Interleukin-2 Receptor alpha Subunit / immunology
  • Lactobacillus reuteri*
  • Lung / metabolism
  • Lung / pathology
  • Mice
  • Mice, Inbred BALB C
  • Probiotics / administration & dosage
  • Probiotics / therapeutic use*
  • Respiratory Hypersensitivity / immunology
  • Respiratory Hypersensitivity / pathology
  • Respiratory Hypersensitivity / therapy*
  • Spleen / immunology
  • Spleen / pathology
  • T-Lymphocytes, Regulatory / immunology*
  • T-Lymphocytes, Regulatory / metabolism
  • T-Lymphocytes, Regulatory / pathology
  • Treatment Outcome

Substances

  • CD4 Antigens
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Interleukin-2 Receptor alpha Subunit