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Journal of Virology, December 2002, p. 12388-12393, Vol. 76, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.23.12388-12393.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Compromised Influenza Virus-Specific CD8+-T-Cell Memory in CD4+-T-Cell-Deficient Mice

Gabrielle T. Belz,1,{dagger} Dominik Wodarz,2,{ddagger} Gabriela Diaz,1 Martin A. Nowak,2 and Peter C. Doherty1*

Department of Immunology, St. Jude Children's Research Hospital, Memphis, Tennessee 38105,1 Program in Theoretical Biology, Institute for Advanced Study, Princeton, New Jersey 085402

Received 13 May 2002/ Accepted 28 August 2002

The primary influenza A virus-specific CD8+-T-cell responses measured by tetramer staining of spleen, lymph node, and bronchoalveolar lavage (BAL) lymphocyte populations were similar in magnitude for conventional I-Ab+/+ and CD4+-T-cell-deficient I-Ab-/- mice. Comparable levels of virus-specific cytotoxic-T-lymphocyte activity were detected in the inflammatory exudate recovered by BAL following challenge. However, both the size of the memory T-cell pool and the magnitude of the recall response in the lymphoid tissues (but not the BAL specimens) were significantly diminished in mice lacking the CD4+ subset. Also, the rate of virus elimination from the infected respiratory tract slowed at low virus loads following challenge of naïve and previously immunized I-Ab-/- mice. Thus, though the capacity to mediate the CD8+-T-cell effector function is broadly preserved in the absence of concurrent CD4+-T-cell help, both the maintenance and recall of memory are compromised and the clearance of residual virus is delayed. These findings are consistent with mathematical models that predict virus-host dynamics in this, and other, models of infection.

* Corresponding author. Mailing address: Department of Immunology, St. Jude Children's Research Hospital, 332 N. Lauderdale, Memphis, TN 38105. Phone: (901) 495-3470. Fax: (901) 495-3107. E-mail: peter.doherty{at}stjude.org.

{dagger} Present address: Division of Immunology, The Walter and Eliza Hall Institute of Medical Research, Melbourne 3050, Australia.

{ddagger} Present address: Fred Hutchinson Cancer Research Center, Seattle, WA 98109.

Journal of Virology, December 2002, p. 12388-12393, Vol. 76, No. 23
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.23.12388-12393.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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