Induction of tumor peptide-specific cytotoxic T cells under serum-free conditions by mature human dendritic cells.
Tumor vaccination strategies using antigen-pulsed dendritic cells (DC) are currently under development. We established an in vitro system using cultured DC from HLA-typed volunteers for the induction of tumor peptide-specific CD8+ T cells. The strength and specificity of the resulting CTL responses were investigated. For stimulation of syngeneic CD8+ T cells two well-defined DC populations were generated: CD1a+ immature DC cultured in the presence of GM-CSF and IL-4 and mature CD83+ DC generated by additional stimulation with a cytokine cocktail. Stimulations were performed under serum-free conditions and in the absence of exogenous cytokines. Analysis of T cell responses showed that mature DC, but not immature DC, were able to induce the expansion of syngeneic tumor peptide-specific CD8+ T cells. Priming of CD8+ T cells with peptide-pulsed mature DC rapidly increased the frequency of antigen-specific T cells (ELISPOT technique). T cells induced by mature DC showed strong antigen-specific cytotoxicity in 51Cr-release assays whereas no antigen-specific cytotoxicity was detectable in CTL generated by immature DC. These data show that terminally differentiated mature DC are necessary for the induction of tumor antigen-specific CTL responses.
Jonuleit
H
H
Department of Dermatology, University of Mainz, Germany. jonuleit@hautklinik.klinik.uni-mainz.de
Giesecke
A
A
Kandemir
A
A
Paragnik
L
L
Knop
J
J
Enk
A H
AH
D015703:Antigens, CD; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D016922:Cellular Senescence; D016895:Culture Media, Serum-Free; D016207:Cytokines / Q000494:pharmacology; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D004338:Drug Combinations; D006801:Humans; D007136:Immunoglobulins / Q000032:analysis; D008562:Membrane Glycoproteins / Q000032:analysis; D009363:Neoplasm Proteins / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology* / Q000502:physiology; D000097802:CD83 Antigen
D015703:Antigens, CD; D016895:Culture Media, Serum-Free; D016207:Cytokines; D004338:Drug Combinations; D007136:Immunoglobulins; D008562:Membrane Glycoproteins; D009363:Neoplasm Proteins; D000097802:CD83 Antigen