Accumulation of regulatory T cells in local draining lymph nodes of the lung correlates with spontaneous resolution of chronic asthma in a murine model.
BACKGROUND
Mice sensitized to ovalbumin develop allergic airway disease (AAD) with short-term aerosol challenge; however, airway inflammation resolves with long-term aerosol challenge, referred to as local inhalational tolerance (LIT).


METHODS
We sought to determine if resolution of airway inflammation correlated with increases in lymphocyte subsets in local lung compartments, including putative regulatory T cells.


RESULTS
At the AAD stage, total numbers of T and B lymphocytes in bronchoalveolar lavage (BAL) were significantly increased above controls; however, at LIT, T and B lymphocytes were significantly reduced compared to AAD. In the lung tissue, the only alteration was a significant increase in CD4+ CD25+ T cells at AAD. In the hilar lymph node (HLN), CD4+ and CD4+ CD25+ T cells were significantly increased at AAD and LIT. In addition, CD8+ T cells were significantly elevated in the HLN at LIT, and CD19+ B cells were significantly increased at AAD. Adoptive transfer of HLN lymphocytes to lymphopenic mice confirmed that AAD lymphocytes could induce airway inflammation in response to aerosol challenge, whereas LIT lymphocytes were unable to do so. Depletion of CD4+ CD25+ T cells in vivo resulted in exacerbation of inflammation at AAD and LIT. CD4+ CD25+ T cells in the HLN also displayed suppressive activity in vitro. Additionally, T cells expressing Foxp3 were increased in the BAL and HLN during LIT.


CONCLUSIONS
These results indicate that lymphocytes with regulatory functions are increased and sustained in local lung compartments at LIT and that their appearance correlates with the resolution of lung inflammation.
Carson
William F
WF
Department of Immunology, University of Connecticut Health Center, Farmington, Conn., USA. wfcarson@umich.edu
Guernsey
Linda A
LA
Singh
Anurag
A
Vella
Anthony T
AT
Schramm
Craig M
CM
Thrall
Roger S
RS
D000336:Aerosols; D000485:Allergens / Q000276:immunology; D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D001249:Asthma / Q000276:immunology* / Q000473:pathology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology; D001992:Bronchoalveolar Lavage Fluid / Q000276:immunology; D015704:CD4 Antigens / Q000378:metabolism; D002452:Cell Count; D049109:Cell Proliferation; D002908:Chronic Disease; D004195:Disease Models, Animal; D005260:Female; D051858:Forkhead Transcription Factors / Q000378:metabolism; D007108:Immune Tolerance; D007249:Inflammation / Q000473:pathology; D053645:Interleukin-2 Receptor alpha Subunit / Q000378:metabolism; D008168:Lung / Q000276:immunology*; D008198:Lymph Nodes / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology; D012130:Respiratory Hypersensitivity / Q000276:immunology* / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000166:cytology / Q000276:immunology* / Q000378:metabolism
D000336:Aerosols; D000485:Allergens; D018941:Antigens, CD19; D015704:CD4 Antigens; C418974:FOXP3 protein, human; D051858:Forkhead Transcription Factors; D053645:Interleukin-2 Receptor alpha Subunit; D010047:Ovalbumin