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J Virol, August 1998, p. 6637-6645, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Protective Role of Gamma Interferon during the Recall Response to Influenza Virus

Adrian Bot,* Simona Bot,dagger and Constantin A. Bona

Department of Microbiology, Mount Sinai School of Medicine, New York, New York 10029

Received 16 March 1998/Accepted 18 May 1998

During secondary immune responses to influenza virus, virus-specific T memory cells are a major source of gamma interferon (IFN-gamma ). We assessed the contribution of IFN-gamma to heterologous protection against the A/WSN/33 (H1N1) virus of wild-type and IFN-gamma -/- mice previously immunized with the A/HK/68 (H3N2) virus. The IFN-gamma -/- mice displayed significantly reduced survival rates subsequent to a challenge with various doses of the A/WSN/33 virus. This was associated with an impaired ability of the IFN-gamma -/- mice to completely clear the pulmonary virus by day 7 after the challenge, although significant reduction of the virus titers was noted. However, the IFN-gamma -/- mice developed type A influenza virus cross-reactive cytotoxic T lymphocytes (CTLs) similar to the wild-type mice, as demonstrated by both cytotoxicity and a limiting-dilution assay for the estimation of CTL precursor frequency. The pulmonary recruitment of T cells in IFN-gamma -/- mice was not dramatically affected, and the percentage of CD4+ and CD8+ T cells was similar to that of wild-type mice. The T cells from IFN-gamma -/- mice did not display a significant switch toward a Th2 profile. Furthermore, the IFN-gamma -/- mice retained the ability to mount significant titers of WSN and HK virus-specific hemagglutination-inhibiting antibodies. Together, these results are consistent with a protective role of IFN-gamma during the heterologous response against influenza virus independently of the generation and local recruitment of cross-reactive CTLs.

* Corresponding author. Present address: Alliance Pharmaceutical Corp., 3030 Science Park Rd., San Diego, CA 92121. Phone: (619) 558-4300. Fax: (619) 678-4178. E-mail: ABot{at}allp.com.

dagger Present address: Alliance Pharmaceutical Corp., San Diego, CA 92121.

J Virol, August 1998, p. 6637-6645, Vol. 72, No. 8
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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