The antiviral CD8+ T cell response is differentially dependent on CD4+ T cell help over the course of persistent infection

Christopher C. Kemball, Christopher D. Pack, Heath M. Guay, Zhu Nan Li, David A. Steinhauer, Eva Szomolanyi-Tsuda, Aron E. Lukacher

Research output: Contribution to journalArticlepeer-review

27 Scopus citations

Abstract

Although many studies have investigated the requirement for CD4+ T cell help for CD8+ T cell responses to acute viral infections that are fully resolved, less is known about the role of CD4+ T cells in maintaining ongoing CD8+ T cell responses to persistently infecting viruses. Using mouse polyoma virus (PyV), we asked whether CD4+ T cell help is required to maintain antiviral CD8+ T cell and humoral responses during acute and persistent phases of infection. Though fully intact during acute infection, the PyV-specific CD8+ T cell response declined numerically during persistent infection in MHC class II-deficient mice, leaving a small antiviral CD8+ T cell population that was maintained long term. These unhelped PyV-specific CD8+ 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+ T cells during persistent infection is impaired in the absence of MHC class II-restricted T cells. In summary, these studies show that CD4+ T cells differentially affect CD8+ T cell responses over the course of a persistent virus infection.

Original languageEnglish (US)
Pages (from-to)1113-1121
Number of pages9
JournalJournal of Immunology
Volume179
Issue number2
DOIs
StatePublished - Jul 15 2007

All Science Journal Classification (ASJC) codes

  • Immunology and Allergy
  • Immunology

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