Cross-Reactivity and Expansion of Dengue-Specific T cells During Acute Primary and Secondary Infections in Humans

Serotype-cross-reactive memory T cells responding to secondary dengue virus (DENV) infection are thought to contribute to disease. However, epitope-specific T cell responses have not been thoroughly compared between subjects with primary versus secondary DENV infection. We studied CD8 + T cells specific for the HLA-A*1101-restricted NS3 133 epitope in a cohort of A11 + DENV-infected patients throughout acute illness and convalescence. We compared the expansion, serotype-cross-reactivity and activation of these cells in PBMC from patients experiencing primary or secondary infection and mild or severe disease by flow cytometry. Our results show expansion and activation of DENV-specific CD8 + T cells during acute infection, which are predominantly serotype-cross-reactive regardless of DENV infection history. These data confirm marked T cell activation and serotype-cross-reactivity during the febrile phase of dengue; however, A11-NS3 133 -specific responses did not correlate with prior antigenic exposure or current disease severity.