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* Department of Pathology and
Department of Microbiology and Immunology, Emory University School of Medicine, Atlanta, GA 30322; and
Department of Pathology, University of Massachusetts Medical School, Worcester, MA 01655
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.
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1 This work was supported by Grants R01CA71971 and R01CA100644 (to A.E.L.), R01CA66644 (to E.S.-T.), AI66870 (to D.A.S.), T32AI007610 (to C.D.P.), and T32AI07272 (to H.M.G.) from the National Institutes of Health.
2 C.C.K. and C.D.P. contributed equally to this work.
3 Current address: Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 North Torrey Pines Road, Mail Code SP30-2110, La Jolla, CA 92037.
4 Address correspondence and reprint requests to Dr. Aron E. Lukacher, Department of Pathology, Emory University School of Medicine, Woodruff Memorial Research Building Room 7307, 101 Woodruff Circle, Atlanta, GA 30322. E-mail address: alukach{at}emory.edu
5 Abbreviations used in this paper: LCMV, lymphocytic choriomeningitis virus; ASC, Ab-secreting cell; 
-HV-68, murine gammaherpesvirus 68; HA, hemagglutinin; LT, large T; MT, middle T; p.i., postinfection; PD-1, programmed death receptor-1; PyV, polyoma virus; CD62L, CD62L-selectin; VV, vaccinia virus.
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