T Cell Reactivity during Infectious Mononucleosis and Persistent Gammaherpesvirus Infection in Mice

• Published in: The Journal of immunology (1950) 2004-03, Vol.172 (5), p.3078-3085
• Main Authors: Flano, Emilio, Hardy, Charles L, Kim, In-Jeong, Frankling, Claire, Coppola, Michael A, Nguyen, Phuong, Woodland, David L, Blackman, Marcia A
• Format: Article
• Language: English
• Subjects: Animals; CD8 antigen; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - virology; Cytotoxicity Tests, Immunologic; Epitopes, T-Lymphocyte - immunology; Female; Gammaherpesvirinae - immunology; Gammaherpesvirus; Immunophenotyping; Infectious Mononucleosis - immunology; Interferon-gamma - metabolism; Kinetics; Ligands; Lymphocyte Activation - immunology; Lymphocyte Count; Mice; Mice, Inbred C57BL; Receptors, Antigen, T-Cell, alpha-beta - biosynthesis; T-Lymphocytes, Regulatory - immunology; T-Lymphocytes, Regulatory - metabolism; T-Lymphocytes, Regulatory - virology; Virus Latency - immunology
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.172.5.3078

Intranasal infection of mice with murine gammaherpesvirus 68 causes a dramatic increase in numbers of activated CD8(+) T cells in the blood, analogous in many respects to EBV-induced infectious mononucleosis in humans. In the mouse model, this lymphocytosis has two distinct components: an early, conventional virus-specific CD8(+) T cell response, and a later response characterized by a dramatic increase among CD8(+) T cells that bear Vbeta4(+) TCRs. We previously demonstrated that Vbeta4(+)CD8(+) T cells recognize an uncharacterized ligand expressed on latently infected B cells in an MHC-independent manner. The frequency of Vbeta4(+)CD8(+) T cells increases dramatically following the peak of viral latency in the spleen. In the current studies, we show that elevated Vbeta4(+)CD8(+) T cell levels are sustained long-term in persistently infected mice, apparently a consequence of continued ligand expression. In addition, we show that Vbeta4(+)CD8(+) T cells can acquire effector functions, including cytotoxicity and the capacity to secrete IFN-gamma, although they have an atypical activation profile compared with well-characterized CD8(+) T cells specific for conventional viral epitopes. The characteristics of Vbeta4(+)CD8(+) T cells (potential effector function, stimulation by latently infected B cells, and kinetics of expansion) suggested that this dominant T cell response plays a key role in the immune control of latent virus. However, Ab depletion and adoptive transfer studies show that Vbeta4(+)CD8(+) T cells are not essential for this function. This murine model of infection may provide insight into the role of unusual populations of activated T cells associated with persistent viral infections.