Soluble proteins and haptens on bone marrow‐derived dendritic cells are presented to host CD4 T cells in an MHC‐restricted manner
Abstract
Because of their potent antigen‐presenting capacity, dendritic cells (DC) have been used extensively in immunotherapy protocols. Our purpose was to functionally characterize mouse bone marrow‐derived DC (BMDC) in vitro (in protein antigen‐ and hapten‐specific assays) and in vivo (injecting soluble protein‐ and hapten‐pulsed DC) to determine their suitability for the generation of T h cell responses. Furthermore, we determined whether there is cross‐presentation on MHC class II molecules during in vivo protein and hapten sensitization. Co‐culture of protein‐pulsed (with hen egg lysozyme (HEL) or with pigeon cytochrome c (CYT)) DC with T cells from HEL‐ or CYT‐ sensitized mice induced antigen‐specific T cell proliferation, but compared to cultured Langerhans cells (LC), BMDC required higher protein antigen‐pulsing concentrations (100 µg and 1 mg/ml). In contrast, at low protein concentrations (10 µg/ml), BMDC stimulated an HEL‐specific hybridoma very efficiently. Using an in vitro T cell proliferation assay and in vivo delayed‐type hypersensitivity and contact sensitivity assays, we found that protein‐ and hapten‐pulsed BMDC were able to sensitize syngeneic but not allogeneic hosts. Furthermore, if we injected BALB/c‐ and C57BL/6‐derived HEL‐pulsed BMDC into F 1 mice, specific secondary proliferation of primed T cells occurred only when antigen‐pulsed stimulator cells syngeneic to the injected BMDC were used. Using this model system we found that soluble proteins and haptens are presented by injected BMDC to host T cells in an MHC‐restricted manner in vivo .