Protection after Vaccination toCell or Antibody Responses but Contribute T + Induction of Dengue Virus-Specific CD 8 T Cells Are Not Required for the + CD 4 Alessandro Sette and Sujan Shresta

Content Provider	Semantic Scholar
Author	Morar, Malika M. Zellweger, Raphaël M. Peters, Bjoern Yauch, Lauren E. Prestwood, Tyler R.
Copyright Year	2010
Abstract	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-a/bR 2/2 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-g, 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. D engue virus (DENV) is a mosquito-borne RNA virus in the Flaviviridae family, which also includes West Nile virus (WNV), yellow fever virus, and Japanese encepha-litis virus. The four serotypes of DENV (DENV1–4) share ∼65– 75% homology at the amino acid level (1). Infections with DENV can be asymptomatic, or cause disease ranging from dengue fever (DF) to dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS) (2). DF is a self-limiting illness with symptoms that include fever, headache, myalgia, retro-orbital pain, nausea, and vomiting. DHF and DSS are characterized by increased vascular permeability, thrombocytopenia, hemorrhagic manifestations, and, in the case of DSS, shock, which can be fatal. The incidence of DENV infections has increased 30-fold in the past 50 y, and DF and DHF/DSS are a significant cause of morbidity and mortality worldwide (2). However, vaccine development has been challenging, as a vaccine should protect against all four DENV serotypes (3). Severe dengue disease (DHF/DSS) most often occurs in individuals experiencing a secondary infection with a heterologous DENV serotype, suggesting the immune response contributes to the …
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Alternate Webpage(s)	http://www.jimmunol.org/content/jimmunol/185/9/5405.full.pdf
Alternate Webpage(s)	http://www.jimmunol.org/content/jimmunol/early/2010/09/24/jimmunol.1001709.full.pdf
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article