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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
| Content Provider | Scilit |
|---|---|
| Author | Yauch, Lauren E. Prestwood, Tyler R. May, Monica M. Morar, Malika M. Zellweger, Raphaël M. Peters, Bjoern Sette, Alessandro Shresta, Sujan |
| Copyright Year | 2010 |
| Description | 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. |
| Ending Page | 5416 |
| Page Count | 12 |
| Starting Page | 5405 |
| ISSN | 00221767 |
| e-ISSN | 15506606 |
| DOI | 10.4049/jimmunol.1001709 |
| Alternate Webpage(s) | http://www.jimmunol.org/content/185/9/5405.full.pdf |
| Journal | The Journal of Immunology |
| Issue Number | 9 |
| Volume Number | 185 |
| Language | English |
| Publisher | The American Association of Immunologists |
| Publisher Date | 2010-11-01 |
| Access Restriction | Open |
| Subject Keyword | Dengue Virus T Cells |
| Content Type | Text |
| Resource Type | Article |
| Subject | Immunology and Allergy Immunology |
