title: Bone marrow-derived macrophage lines and immortalized cloned macrophage and dendritic cells support priming of Borrelia burgdorferi--specific T cell responses in vitro and/or in vivo.
abstract: In vitro propagated bone marrow-derived macrophage populations (BMMO) as well as cloned immortalized macrophage (MT2/1) and dendritic (D2SC/1) cell lines were analyzed for their capacity to promote activation and/or proliferation of naïve T cells to Borrelia burgdorferi antigens in vitro and in vivo. All three cell types constitutively express high levels of MHC class I structures as well as the co-stimulatory molecules B7/BB1 and heat-stable antigen (HSA); MHC class II molecules (I-A) are upregulated following incubation with either intact spirochetes or the purified lipoprotein OspA (Lip-OspA) but not with its delipidated from (MDP-OspA). Only BMMO were able to induce proliferation of naïve T cells or T cells derived from infected mice to intact spirochetes in vitro. However, all three accessory populations could support primary and secondary T cell responses to Lip-OspA but not, or only marginally, to MDP-OspA under similar conditions. The number of accessory cells required for optimal stimulation of naïve or pre-sensitized T cells was approximately 3 x lower for D2SC 1 than for BMMO or MT2/1. In addition, BMMO pre-pulsed with Lip-OspA were able to prime T cells in vivo, indicating a crucial role for the lipid moiety in antigen presentation. From two truncated lipopeptides of Lip-OspA containing either 20 or 6 aminoterminal residues, only Lip-OspApep20 but not Lip-OspApep6 induced significant proliferation in naïve for pre-sensitized T cells in vitro, suggesting that T cells mainly respond to the protein rather than the lipid moiety of OspA. Thus, the data demonstrate that BMMO, MT2/1 and D2SC/1 have differential capacities to prime spirochete-reactive T cells and to support their growth in vitro, suggesting that optimal activation and propagation of T cells also depends on the quality of the antigen.
authors.affiliation: Max-Planck-Institut für Immunobiology, Freiburg, Germany.
authors.forename: U
authors.initials: U
authors.lastname: Altenschmidt
authors.forename: P
authors.initials: P
authors.lastname: Ricciardi-Castagnoli
authors.forename: M
authors.initials: M
authors.lastname: Modolell
authors.forename: H
authors.initials: H
authors.lastname: Otto
authors.forename: K H
authors.initials: KH
authors.lastname: Wiesmüller
authors.forename: G
authors.initials: G
authors.lastname: Jung
authors.forename: M M
authors.initials: MM
authors.lastname: Simon
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000954:Antigens, Surface / Q000276:immunology; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology; D001428:Bacterial Vaccines; D001854:Bone Marrow Cells; D015748:Borrelia burgdorferi Group / Q000276:immunology*; D002460:Cell Line; D002999:Clone Cells; D005260:Female; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D007114:Immunization; D008074:Lipoproteins; D008264:Macrophages / Q000166:cytology* / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000954:Antigens, Surface; D001425:Bacterial Outer Membrane Proteins; D001428:Bacterial Vaccines; D000949:Histocompatibility Antigens Class II; D008074:Lipoproteins; C072045:OspA protein