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Journal of Virology, July 2004, p. 6836-6845, Vol. 78, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.13.6836-6845.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Critical Role of CD4 T Cells in an Antibody-Independent Mechanism of Vaccination against Gammaherpesvirus Latency

James Scott McClellan, Scott A. Tibbetts, Shivaprakash Gangappa, Kelly A. Brett, and Herbert W. Virgin IV*

Department of Pathology and Immunology and Department of Molecular Microbiology, Washington University School of Medicine, St. Louis, Missouri 63110

Received 8 December 2003/ Accepted 5 April 2004

We have previously demonstrated that it is possible to effectively vaccinate against long-term murine gammaherpesvirus 68 ({gamma}HV68) latency by using a reactivation-deficient virus as a vaccine (S. A. Tibbetts, J. S. McClellan, S. Gangappa, S. H. Speck, and H. W. Virgin IV, J. Virol. 77:2522-2529, 2003). Immune antibody was capable of recapitulating aspects of this vaccination. This led us to determine whether antibody is required for vaccination against latency. Using mice lacking antigen-specific antibody responses, we demonstrate here that antibody and B cells are not required for vaccination against latency. We also show that surveillance of latent infection in normal animals depends on CD4 and CD8 T cells, suggesting that T cells might be capable of preventing the establishment of latency. In the absence of an antibody response, CD4 T cells but not CD8 T cells are required for effective vaccination against latency in peritoneal cells, while either CD4 or CD8 T cells can prevent the establishment of splenic latency. Therefore, CD4 T cells play a critical role in immune surveillance of gammaherpesvirus latency and can mediate vaccination against latency in the absence of antibody responses.

* Corresponding author. Mailing address: Department of Pathology and Immunology, Washington University School of Medicine, 660 S. Euclid Ave., Box 8118, St. Louis, MO 63110. Phone: (314) 362-9223. Fax: (314) 362-4096. E-mail: virgin{at}wustl.edu.

Journal of Virology, July 2004, p. 6836-6845, Vol. 78, No. 13
0022-538X/04/$08.00+0     DOI: 10.1128/JVI.78.13.6836-6845.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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