CD4+ T cells are not required for the induction of dengue virus-specific CD8+ T cell or antibody responses but contribute to protection after vaccination

• Published in: The Journal of immunology (1950) Vol. 185; no. 9; pp. 5405 - 5416
• Main Authors: Yauch, Lauren E, Prestwood, Tyler R, May, Monica M, Morar, Malika M, Zellweger, Raphaël M, Peters, Bjoern, Sette, Alessandro, Shresta, Sujan
• Format: Journal Article
• Language: English
• Published: United States 01-11-2010
• Subjects: Animals; Antibodies, Viral - blood; Antibodies, Viral - immunology; Antigens, Viral - immunology; CD4-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - immunology; Dengue - blood; Dengue - immunology; Dengue Vaccines - immunology; Dengue Virus - immunology; Enzyme-Linked Immunosorbent Assay; Epitopes, T-Lymphocyte - immunology; Flow Cytometry; Immunohistochemistry; Lymphocyte Activation - immunology; Mice; Mice, Inbred C57BL; Mice, Knockout; Viral Load
• ISSN: 0022-1767; 1550-6606; 1550-6606
• DOI: 10.4049/jimmunol.1001709

The contribution of T cells to the host response to dengue virus (DENV) infection is not well understood. We previously demonstrated a protective role for CD8(+) T cells during primary DENV infection using a mouse-passaged DENV strain and IFN-α/βR(-/-) C57BL/6 mice, which are susceptible to DENV infection. In this study, we examine the role of CD4(+) T cells during primary DENV infection. Four I-A(b)-restricted epitopes derived from three of the nonstructural DENV proteins were identified. CD4(+) T cells expanded and were activated after DENV infection, with peak activation occurring on day 7. The DENV-specific CD4(+) T cells expressed intracellular IFN-γ, TNF, IL-2, and CD40L, and killed peptide-pulsed target cells in vivo. Surprisingly, depletion of CD4(+) T cells before DENV infection had no effect on viral loads. Consistent with this observation, CD4(+) T cell depletion did not affect the DENV-specific IgG or IgM Ab titers or their neutralizing activity, or the DENV-specific CD8(+) T cell response. However, immunization with the CD4(+) T cell epitopes before infection resulted in significantly lower viral loads. Thus, we conclude that whereas CD4(+) T cells are not required for controlling primary DENV infection, their induction by immunization can contribute to viral clearance. These findings suggest inducing anti-DENV CD4(+) T cell responses by vaccination may be beneficial.