Similar immune responses and antitumor effects of murine dendritic cells loaded with either exogenous or endogenous-synthesized protein.
Conceptually, dendritic cells (DCs) take up and process exogenous antigens that are presented on MHC (major histocompatibility complex) class II molecules to stimulate CD4+ T cells, and present endogenously-produced proteins to CD8+ T cells through an MHC class I-dependent pathway. In this study, we compared the antitumor effects generated in vivo after vaccinations with DCs either loaded with exogenous protein (DCs-exo) or presenting antigens derived from endogenous-synthesized protein (DCs-endo). We used the murine MC26SC31 colon carcinoma cell line expressing on the cell surface the human CD4 (hCD4) molecule as a model tumor-associated antigen (TAA). Bone marrow (BM)-derived DCs-endo were obtained from histocompatible transgenic mice constitutively expressing hCD4; BM-derived DCs-exo were obtained after in vitro loading DCs, from syngenic normal mice, with purified soluble hCD4 protein (shCD4). Altogether, our results show that intravenous (i.v.) administration of DCs-exo and DCs-endo can trigger similar cytotoxic and humoral protecting immune responses against a lethal tumor challenge. hCD4 antigen-specific T cell-mediated cytotoxic immune response was not accompanied by elevated INF-gamma serum levels. This suggests, in the case of DCs-exo, a possible in vivo CTL cross-priming triggering a CD8+ T cell-mediated immune response in the absence of de novo antigen synthesis within the DCs.
Lacave
Roger
R
Laboratoire de Biologie et Thérapeutique des Pathologies Immunitaires, CNRS UMR 7087/UPMC, Hôpital de la Pitié, Paris, France.
Masurier
Carole
C
Guigon
Martine
M
Lemoine
François M
FM
Klatzmann
David
D
Colombo
Bruno M
BM
D000818:Animals; D017951:Antigen Presentation; D000970:Antineoplastic Agents / Q000494:pharmacology; D015704:CD4 Antigens / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism; D003713:Dendritic Cells / Q000276:immunology*; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007167:Immunotherapy / Q000379:methods*; D016219:Immunotherapy, Adoptive; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009369:Neoplasms / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors
D000970:Antineoplastic Agents; D015704:CD4 Antigens