Published online before print November 8, 2007

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(American Journal of Pathology. 2007;171:1944-1951.)
© 2007 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2007.070578

Respiratory Virus-Induced Regulation of Asthma-Like Responses in Mice Depends upon CD8 T Cells and Interferon- Production

Joost J. Smit^*, Louis Boon and Nicholas W. Lukacs^*

From the Department of Pathology,^* University of Michigan Medical School, Ann Arbor, Michigan; and Bioceros, Utrecht, The Netherlands

Respiratory virus infections can significantly influence the development of airway disease by both predisposing and exacerbating the developing lung immune environment. In contrast, the initiation of a more desirable anti-viral response may better prepare the local environment and protect it from developing an adverse long-term disease phenotype. BALB/c or C57BL/6 mice exposed to respiratory syncytial virus (RSV) infection at the same time as allergen sensitization were assessed for airway function, cytokine responses, and inflammatory parameters. Depending on the genetic strain of mouse used, BALB/c versus C57BL/6, RSV could differentially protect against the development of airway allergen responses. Although RSV was able to block allergen sensitization and induction of airway hyperresponsiveness and eosinophilic inflammation in C57BL/6 mice, the infection did not reduce the allergic responses in BALB/c mice. The alteration of airway responsiveness did not depend on the timing of RSV infection in C57BL/6 mice in conjunction to the allergen sensitization protocol. Neutralization experiments demonstrated that interferon- contributed significantly to the RSV-induced airway attenuation of the allergic responses, whereas transfer of CD8 T cells from RSV-infected animals suggested that they were partially responsible for the altered environment. These data suggest that a respiratory viral infection impacts on the local lung environment and may reflect specific aspects of the hygiene hypothesis. However, the outcome of this interaction depends on the immunological response of the host.