Bone marrow-generated dendritic cells pulsed with a class I-restricted peptide are potent inducers of cytotoxic T lymphocytes.
It has previously been shown that bone marrow-generated dendritic cells (DC) are potent stimulators in allogeneic mixed leukocyte reactions and are capable of activating naive CD4+ T cells in situ in an antigen-specific manner. In this study we have investigated whether bone marrow-generated DC are capable of inducing antigen-specific CD8+ T cell responses in vivo. Initial attempts to induce specific cytotoxic T lymphocyte (CTL) responses in mice injected with bone marrow-generated DC pulsed with ovalbumin (OVA) peptide were frustrated by the presence of high levels of nonspecific lytic activity, which obscured, though not completely, the presence of Ag-specific CTL. Using conditions that effectively differentiate between antigen-specific and nonspecific lytic activity, we have shown that bone marrow-generated DC pulsed with OVA peptide are potent inducers of OVA-specific CTL responses in vivo, compared with splenocytes or RMA-S cells pulsed with OVA peptide, or compared with immunization with free OVA peptide mixed with adjuvant. Antibody-mediated depletion experiments have shown that the cytotoxic effector cells consist primarily of CD8+ cells, and that induction of CTL in vivo is dependent on CD4+ as well as on CD8+ T cells. These results provide the basis for exploring the role of bone marrow-generated DC in major histocompatibility class I-restricted immune responses, and they provide the rationale for using bone marrow-generated DC in CTL-mediated immunotherapy of cancer and infectious diseases.
Porgador
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A
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Gilboa
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E
D000276:Adjuvants, Immunologic; D000818:Animals; D017951:Antigen Presentation; D000941:Antigens / Q000276:immunology* / Q000378:metabolism; D001854:Bone Marrow Cells; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D000939:Epitopes / Q000276:immunology; D005260:Female; D006183:H-2 Antigens / Q000276:immunology*; D007114:Immunization; D016130:Immunophenotyping; D008223:Lymphoma / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D010047:Ovalbumin / Q000276:immunology* / Q000378:metabolism; D010446:Peptide Fragments / Q000276:immunology*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D014407:Tumor Cells, Cultured
D000276:Adjuvants, Immunologic; D000941:Antigens; D000939:Epitopes; D006183:H-2 Antigens; D010446:Peptide Fragments; D010047:Ovalbumin