De novo T-lymphocyte responses against baculovirus-derived recombinant influenzavirus hemagglutinin generated by a naive umbilical cord blood model of dendritic cell vaccination.
Cancer patients and recipients of hematopoietic stem cell transplantation exhibit a negligible response to influenza vaccine. Toward the goal of addressing this issue, we developed an in vitro model of dendritic cell (DC) immunotherapy utilizing DCs generated from naïve umbilical cord blood (UCB). UCB DCs were loaded with purified rHA protein and used to stimulate autologous T-lymphocytes. Upon recall with HA-loaded autologous DC, a 4-10-fold increase in the number of IFN-gamma producing T-lymphocytes was observed in comparison to T-cells stimulated with control DCs. Antigen-specific T-cell functionality was determined by (51)Cr lytic assay. Using a peptide library of predicted HA binding epitopes, we mapped an HA-specific, DR15-restricted CD4 T-cell epitope and observed tetramer positive cells. This model demonstrates that HA-specific immune responses might possibly be generated in a de novo fashion and suggests that dendritic cell immunotherapy for the prevention of influenza in populations of immunosuppressed individuals could be feasible.
Safdar
Amar
A
Department of Infectious Diseases, Infection Control, and Employee Health, University of Texas, M.D. Anderson Cancer Center, Houston, TX 77030, United States. asafdar@mdanderson.org
Decker
William K
WK
Li
Sufang
S
Xing
Dongxia
D
Robinson
Simon N
SN
Yang
Hong
H
Steiner
David
D
Rodriguez
Gilhen
G
Shpall
Elizabeth J
EJ
Bollard
Catherine
C
D016367:Baculoviridae / Q000235:genetics; D003713:Dendritic Cells / Q000276:immunology*; D005312:Fetal Blood / Q000166:cytology* / Q000276:immunology*; D019267:Hemagglutinin Glycoproteins, Influenza Virus / Q000235:genetics / Q000276:immunology*; D006801:Humans; D007111:Immunity, Cellular; D066298:In Vitro Techniques; D007231:Infant, Newborn; D007252:Influenza Vaccines / Q000235:genetics / Q000276:immunology; D018448:Models, Immunological; D011994:Recombinant Proteins / Q000235:genetics / Q000276:immunology; D013601:T-Lymphocytes / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D019267:Hemagglutinin Glycoproteins, Influenza Virus; D007252:Influenza Vaccines; D011994:Recombinant Proteins