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Allogeneic Differences in the Dependence on CD4⁺ T-Cell Help for Virus-Specific CD8⁺ T-Cell Differentiation

Christopher C. Kemball,^1, Eva Szomolanyi-Tsuda,² and Aron E. Lukacher^1*

Department of Pathology, Emory University School of Medicine, Woodruff Memorial Research Building, Room 7307, 101 Woodruff Circle, Atlanta, Georgia 30322,¹ Department of Pathology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, Massachusetts 01655²

Received 13 August 2007/ Accepted 24 September 2007

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 allogeneic strains of inbred mice.

Published ahead of print on 3 October 2007.

Present address: Molecular and Integrative Neurosciences Department, The Scripps Research Institute, 10550 North Torrey Pines Road, Mail Code SP30-2110, La Jolla, CA 92037.