Similar immune responses and antitumor effects of murine dendritic cells loaded with either exogenous or...

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.