Critical role of CD4 T cells in an antibody-independent mechanism of vaccination against gammaherpesvirus latency.
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.
McClellan
James Scott
JS
Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110, USA.
Tibbetts
Scott A
SA
Gangappa
Shivaprakash
S
Brett
Kelly A
KA
Virgin
Herbert W
HW
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*
D000914:Antibodies, Viral; D022283:Herpesvirus Vaccines