title: Critical role of CD4 T cells in an antibody-independent mechanism of vaccination against gammaherpesvirus latency.
abstract: 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.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: James Scott
authors.initials: JS
authors.lastname: McClellan
authors.forename: Scott A
authors.initials: SA
authors.lastname: Tibbetts
authors.forename: Shivaprakash
authors.initials: S
authors.lastname: Gangappa
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Brett
authors.forename: Herbert W
authors.initials: HW
authors.lastname: Virgin
mesh_terms: D000818:Animals; D000914:Antibodies, Viral / Q000378:metabolism*; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D018142:Gammaherpesvirinae / Q000235:genetics / Q000276:immunology* / Q000502:physiology; D006566:Herpesviridae Infections / Q000276:immunology / Q000517:prevention & control*; D022283:Herpesvirus Vaccines / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D014611:Vaccination; D017735:Virus Latency / Q000276:immunology*
chemical_list: D000914:Antibodies, Viral; D022283:Herpesvirus Vaccines