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dc.contributor.authorMangada, Maloy M.
dc.contributor.authorRothman, Alan L.
dc.date2022-08-11T08:09:31.000
dc.date.accessioned2022-08-23T16:33:56Z
dc.date.available2022-08-23T16:33:56Z
dc.date.issued2005-08-06
dc.date.submitted2009-03-10
dc.identifier.citation<p>J Immunol. 2005 Aug 15;175(4):2676-83.</p>
dc.identifier.issn0022-1767 (Print)
dc.identifier.doi10.4049/jimmunol.175.4.2676
dc.identifier.pmid16081844
dc.identifier.urihttp://hdl.handle.net/20.500.14038/38217
dc.description.abstractThe 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.
dc.language.isoen_US
dc.relation<p><a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=16081844&dopt=Abstract">Link to Article in PubMed</a></p>
dc.relation.urlhttps://doi.org/10.4049/jimmunol.175.4.2676
dc.subjectAmino Acid Sequence
dc.subjectCD4-Positive T-Lymphocytes
dc.subjectCytokines
dc.subjectDengue Virus
dc.subjectEpitopes, T-Lymphocyte
dc.subjectHLA-D Antigens
dc.subjectHumans
dc.subjectMolecular Sequence Data
dc.subjectPeptide Fragments
dc.subjectSerine Endopeptidases
dc.subjectSerotyping
dc.subjectStaining and Labeling
dc.subjectVaccines, Attenuated
dc.subjectViral Vaccines
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleAltered cytokine responses of dengue-specific CD4+ T cells to heterologous serotypes
dc.typeJournal Article
dc.source.journaltitleJournal of immunology (Baltimore, Md. : 1950)
dc.source.volume175
dc.source.issue4
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/oapubs/1095
dc.identifier.contextkey770073
html.description.abstract<p>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.</p>
dc.identifier.submissionpathoapubs/1095
dc.contributor.departmentCenter for Infectious Disease and Vaccine Research
dc.source.pages2676-83


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