Altered cytokine responses of dengue-specific CD4+ T cells to heterologous serotypes

UMMS Affiliation

Center for Infectious Disease and Vaccine Research

Publication Date


Document Type



Amino Acid Sequence; CD4-Positive T-Lymphocytes; Cytokines; Dengue Virus; Epitopes, T-Lymphocyte; HLA-D Antigens; Humans; Molecular Sequence Data; Peptide Fragments; Serine Endopeptidases; Serotyping; Staining and Labeling; Vaccines, Attenuated; Viral Vaccines


Life Sciences | Medicine and Health Sciences


The interplay of different inflammatory cytokines induced during a dengue (DEN) virus infection plays a role in either protection or increased disease severity. We measured the frequencies and characterized the cytokine responses of DEN virus-specific memory CD4+ T cells in PBMC of six volunteers who received experimental live attenuated monovalent DEN vaccines. IFN-gamma and TNF-alpha responses to inactivated DEN Ags were detected in up to 0.54 and 1.17% of total circulating CD4+ T cells, respectively. Ags from the homologous serotype elicited the highest IFN-gamma response. The ratio of TNF-alpha- to IFN-gamma-producing CD4+ T cells was higher after stimulation with Ags from heterologous DEN serotypes. Peptide-specific CD4+ T cell frequencies of up to 0.089% were detected by direct staining using HLA class II tetramers. IFN-gamma and TNF-alpha responses to individual HLA class II-restricted peptide epitopes were detected in up to 0.05 and 0.27% of CD4+ T cells, respectively. Peptide sequences from the homologous serotype elicited a variety of cytokine response patterns. TNF-alpha- to IFN-gamma-positive CD4+ T cell ratios varied between peptides, but the ratio of the sum of responses was highest against heterologous serotypes. These results demonstrate epitope sequence-specific differences in T cell effector function. These patterns of effector responses may play a role in the immunopathogenesis of DEN hemorrhagic fever.

DOI of Published Version



J Immunol. 2005 Aug 15;175(4):2676-83.

Journal/Book/Conference Title

Journal of immunology (Baltimore, Md. : 1950)

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Link to Article in PubMed

PubMed ID