Soluble proteins and haptens on bone marrow-derived dendritic cells are presented to host CD4 T cells in an MHC-restricted manner.
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 microg and 1 mg/ml). In contrast, at low protein concentrations (10 microg/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 F1 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.
Olasz
Edit B
EB
Dermatology Branch, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-1908, USA.
Linton
Jay
J
Katz
Stephen I
SI
D000818:Animals; D017951:Antigen Presentation; D001854:Bone Marrow Cells / Q000166:cytology*; D003574:Cytochrome c Group / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology*; D004527:Egg Proteins / Q000276:immunology; D005260:Female; D006241:Haptens / Q000737:chemistry / Q000276:immunology*; D006649:Histocompatibility Antigens / Q000502:physiology*; D006825:Hybridomas / Q000378:metabolism; D006968:Hypersensitivity, Delayed / Q000276:immunology; D015847:Interleukin-4 / Q000378:metabolism; D007801:Langerhans Cells / Q000276:immunology; D008562:Membrane Glycoproteins / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D010853:Picryl Chloride / Q000276:immunology; D011506:Proteins / Q000378:metabolism; D012995:Solubility; D016176:T-Lymphocyte Subsets / Q000276:immunology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology*
D003574:Cytochrome c Group; D004527:Egg Proteins; D006241:Haptens; D006649:Histocompatibility Antigens; D008562:Membrane Glycoproteins; D011506:Proteins; D015847:Interleukin-4; D010853:Picryl Chloride