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J. Virol. doi:10.1128/JVI.01778-07
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

Allogeneic differences in the dependence on CD4⁺ T cell help for virus-specific CD8⁺ T cell differentiation

Department of Pathology, Emory University School of Medicine, Woodruff Memorial Research Building, Room 7307, 101 Woodruff Circle, Atlanta, GA 30322; Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655

^* To whom correspondence should be addressed. Email: alukach{at}emory.edu.

	Abstract

CD4⁺ T cell help enables antiviral CD8⁺ T cells to differentiate into fully competent memory cells and sustains CD8⁺ T cell-mediated immunity during persistent virus infection. We recently reported that mice of C57BL/6 and C3H strains differ in their dependence on CD28 and CD40L costimulation for long-term control of infection by polyoma virus, a persistent mouse pathogen. In this study, we asked whether mice of these inbred strains also vary in their requirement for CD4⁺ T cell help for generating and maintaining polyoma virus-specific CD8⁺ T cells. CD4⁺ T cell-depleted C57BL/6 mice mounted a robust antiviral CD8⁺ T cell response during acute infection, whereas unhelped CD8⁺ T cell effectors in C3H mice were functionally impaired during acute infection and failed to expand upon antigenic challenge during persistent infection. Using (C57BL/6 x C3H) F1 mice, we found that the dispensability for CD4⁺ T cell help for the H-2^b-restricted polyoma virus-specific CD8⁺ T cell response during acute infection extends to the H-2^k-restricted antiviral CD8⁺ T cells. Our findings demonstrate that dependence on CD4⁺ T cell help for antiviral CD8⁺ T cell effector differentiation can vary among strains of inbred mice.