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Journal of Virology, October 2005, p. 12703-12713, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12703-12713.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Rapid Recruitment of Virus-Specific CD8 T Cells Restructures Immunodominance during Protective Secondary Responses

Anne E. Tebo, Michael J. Fuller, Dalia E. Gaddis, Kyoko Kojima, Kunal Rehani, and Allan J. Zajac*

Department of Microbiology, University of Alabama at Birmingham, Birmingham, Alabama 35294-2170

Received 8 April 2005/ Accepted 18 July 2005

In this study we investigate the attributes of virus-specific memory CD8 T cells which most effectively control secondary infections. By rechallenging mice that had cleared primary lymphocytic choriomeningitis virus infections, we revealed that the secondary response is remarkably swift. Within 6 h following secondary infection, the production of gamma interferon becomes detectable directly ex vivo. During this protective phase of the secondary response, a very early elaboration of effector activities is preferentially exhibited by T cells specific for the viral NP396 epitope. This wave of activation contains the infection primarily before the initiation of the proliferative phase of the secondary response. Marked expansion is observed, but its magnitude differs depending on the epitope specificity of the responding cells; between 42 and 48 h following infection, ~70% of NP396-specific memory cells are in the S phase of the cell cycle, as assessed by bromodeoxyuridine incorporation studies. Epitope-dependent differences during the proliferative phase of the secondary response were confirmed by adoptive transfer studies with CFSE-labeled T cells. Although NP396-specific T cells typically dominate secondary responses, the broader multiepitope-specific population of antiviral T cells is beneficial for controlling a variant virus with an escape mutation in this epitope. These findings indicate that the induction and maintenance of a focused response contribute to the clearance of secondary infections; however, a more diverse pool of antiviral T cells facilitates long-term immunity to mutable pathogens.

* Corresponding author. Mailing address: Department of Microbiology, University of Alabama at Birmingham, 845 Nineteenth Street South, 446 BBRB, Birmingham, AL 35294-2170. Phone: (205) 975-5644. Fax: (205) 975-5645. E-mail: azajac{at}uab.edu.

Journal of Virology, October 2005, p. 12703-12713, Vol. 79, No. 20
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.20.12703-12713.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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