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J Clin Invest. 2011 Jan;121(1):57-69. doi: 10.1172/JCI44845. Epub 2010 Dec 13.

Influenza infection in suckling mice expands an NKT cell subset that protects against airway hyperreactivity.

Author information

1
Division of Immunology and Allergy, Children’s Hospital, Harvard Medical School, Boston, Massachusetts, USA.

Abstract

Infection with influenza A virus represents a major public health threat worldwide, particularly in patients with asthma. However, immunity induced by influenza A virus may have beneficial effects, particularly in young children, that might protect against the later development of asthma, as suggested by the hygiene hypothesis. Herein, we show that infection of suckling mice with influenza A virus protected the mice as adults against allergen-induced airway hyperreactivity (AHR), a cardinal feature of asthma. The protective effect was associated with the preferential expansion of CD4-CD8-, but not CD4+, NKT cells and required T-bet and TLR7. Adoptive transfer of this cell population into allergen-sensitized adult mice suppressed the development of allergen-induced AHR, an effect associated with expansion of the allergen-specific forkhead box p3+ (Foxp3+) Treg cell population. Influenza-induced protection was mimicked by treating suckling mice with a glycolipid derived from Helicobacter pylori (a bacterium associated with protection against asthma) that activated NKT cells in a CD1d-restricted fashion. These findings suggest what we believe to be a novel pathway that can regulate AHR, and a new therapeutic strategy (treatment with glycolipid activators of this NKT cell population) for asthma.

PMID:
21157038
PMCID:
PMC3007162
DOI:
10.1172/JCI44845
[Indexed for MEDLINE]
Free PMC Article

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