PMID- 8371350 OWN - NLM STAT- MEDLINE DCOM- 19931012 LR - 20200724 IS - 0022-538X (Print) IS - 1098-5514 (Electronic) IS - 0022-538X (Linking) VI - 67 IP - 10 DP - 1993 Oct TI - Dengue virus-specific human CD4+ T-lymphocyte responses in a recipient of an experimental live-attenuated dengue virus type 1 vaccine: bulk culture proliferation, clonal analysis, and precursor frequency determination. PG - 5962-7 AB - We analyzed the CD4+ T-lymphocyte responses to dengue, West Nile, and yellow fever viruses 4 months after immunization of a volunteer with an experimental live-attenuated dengue virus type 1 vaccine (DEN-1 45AZ5). We examined bulk culture proliferation to noninfectious antigens, determined the precursor frequency of specific CD4+ T cells by limiting dilution, and established and analyzed CD4+ T-cell clones. Bulk culture proliferation was predominantly dengue virus type 1 specific with a lesser degree of cross-reactive responses to other dengue virus serotypes, West Nile virus, and yellow fever virus. Precursor frequency determination by limiting dilution in the presence of noninfectious dengue virus antigens revealed a frequency of antigen-reactive cells of 1 in 1,686 peripheral blood mononuclear cells (PBMC) for dengue virus type 1, 1 in 9,870 PBMC for dengue virus type 3, 1 in 14,053 PBMC for dengue virus type 2, and 1 in 17,690 PBMC for dengue virus type 4. Seventeen CD4+ T-cell clones were then established by using infectious dengue virus type 1 as antigen. Two patterns of dengue virus specificity were found in these clones. Thirteen clones were dengue virus type 1 specific, and four clones recognized both dengue virus types 1 and 3. Analysis of human leukocyte antigen (HLA) restriction revealed that five clones are HLA-DRw52 restricted, one clone is HLA-DP3 restricted, and one clone is HLA-DP4 restricted. These results indicate that in this individual, the CD4+ T-lymphocyte responses to immunization with live-attenuated dengue virus type 1 vaccine are predominantly serotype specific and suggest that a multivalent vaccine may be necessary to elicit strong serotype-cross-reactive CD4+ T-lymphocyte responses in such individuals. FAU - Green, S AU - Green S AD - Department of Medicine, University of Massachusetts Medical Center, Worcester 01655. FAU - Kurane, I AU - Kurane I FAU - Edelman, R AU - Edelman R FAU - Tacket, C O AU - Tacket CO FAU - Eckels, K H AU - Eckels KH FAU - Vaughn, D W AU - Vaughn DW FAU - Hoke, C H Jr AU - Hoke CH Jr FAU - Ennis, F A AU - Ennis FA LA - eng GR - R01-AI30624/AI/NIAID NIH HHS/United States GR - T32-A107272/PHS HHS/United States PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - J Virol JT - Journal of virology JID - 0113724 RN - 0 (Antibodies, Monoclonal) RN - 0 (Antigens, CD) RN - 0 (Antigens, Viral) RN - 0 (CD3 Complex) RN - 0 (CD4 Antigens) RN - 0 (HLA-D Antigens) RN - 0 (Vaccines, Attenuated) RN - 0 (Viral Vaccines) SB - IM MH - Adult MH - Antibodies, Monoclonal MH - Antigens, CD/*analysis MH - Antigens, Viral/immunology MH - CD3 Complex/analysis MH - CD4 Antigens/*analysis MH - Cells, Cultured MH - Clone Cells MH - *Cytotoxicity, Immunologic MH - Dengue Virus/classification/*immunology MH - HLA-D Antigens/immunology MH - Humans MH - *Lymphocyte Activation MH - Lymphocytes/*microbiology MH - Male MH - Serotyping MH - T-Lymphocyte Subsets/*immunology MH - Vaccines, Attenuated/*immunology MH - Viral Vaccines/*immunology PMC - PMC238017 EDAT- 1993/10/01 00:00 MHDA- 2001/03/28 10:01 PMCR- 1993/10/01 CRDT- 1993/10/01 00:00 PHST- 1993/10/01 00:00 [pubmed] PHST- 2001/03/28 10:01 [medline] PHST- 1993/10/01 00:00 [entrez] PHST- 1993/10/01 00:00 [pmc-release] AID - 10.1128/JVI.67.10.5962-5967.1993 [doi] PST - ppublish SO - J Virol. 1993 Oct;67(10):5962-7. doi: 10.1128/JVI.67.10.5962-5967.1993.