The Antiviral CD8 super(+) T Cell Response Is Differentially Dependent on CD4 super(+) T Cell Help Over the Course of Persistent Infection

• Published in: Journal of Immunology Vol. 179; no. 2; pp. 1113 - 1121
• Main Authors: Kemball, Christopher C, Pack, Christopher D, Guay, Heath M, Li, Zhu-Nan, Steinhauer, David A, Szomolanyi-Tsuda, Eva, Lukacher, Aron E
• Format: Journal Article
• Language: English
• Published: 01-07-2007
• Subjects: Polyomavirus
• ISSN: 0022-1767; 1365-2567

Although many studies have investigated the requirement for CD4 super(+) T cell help for CD8 super(+) T cell responses to acute viral infections that are fully resolved, less is known about the role of CD4 super(+) T cells in maintaining ongoing CD8 super(+) T cell responses to persistently infecting viruses. Using mouse polyoma virus (PyV), we asked whether CD4 super(+) T cell help is required to maintain antiviral CD8 super(+) T cell and humoral responses during acute and persistent phases of infection. Though fully intact during acute infection, the PyV-specific CD8 super(+) T cell response declined numerically during persistent infection in MHC class II-deficient mice, leaving a small antiviral CD8 super(+) T cell population that was maintained long term. These unhelped PyV-specific CD8 super(+) T cells were functionally unimpaired; they retained the potential for robust expansion and cytokine production in response to Ag rechallenge. In addition, although a strong antiviral IgG response was initially elicited by MHC class II-deficient mice, these Ab titers fell, and long-lived PyV-specific Ab-secreting cells were not detected in the bone marrow. Finally, using a minimally myeloablative mixed bone marrow chimerism approach, we demonstrate that recruitment and/or maintenance of new virus-specific CD8 super(+) T cells during persistent infection is impaired in the absence of MHC class II-restricted T cells. In summary, these studies show that CD4 super(+) T cells differentially affect CD8 super(+) T cell responses over the course of a persistent virus infection.