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
Authors
Green, SharoneKurane, Ichiro
Edelman, Robert
Tacket, Carol 0.
Eckels, Kenneth H.
Vaughn, David W.
Hoke, Charles H.
Ennis, Francis A.
UMass Chan Affiliations
Department of Medicine, Division of Infectious Diseases and ImmunologyDocument Type
Journal ArticlePublication Date
1993-10-01Keywords
AdultAntibodies, Monoclonal
Antigens, CD
Antigens, CD3
Antigens, CD4
Antigens, Viral
Cells, Cultured
Clone Cells
*Cytotoxicity, Immunologic
Dengue Virus
HLA-D Antigens
Humans
*Lymphocyte Activation
Lymphocytes
Male
Serotyping
T-Lymphocyte Subsets
Vaccines, Attenuated
Viral Vaccines
Life Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
J Virol. 1993 Oct;67(10):5962-7.
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http://hdl.handle.net/20.500.14038/38702PubMed ID
8371350Related Resources
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