title: Infectious nickel tolerance: a reciprocal interplay of tolerogenic APCs and T suppressor cells that is driven by immunization.
abstract: Previously, we reported that tolerance to nickel, induced by oral administration of Ni(2+) ions, can be adoptively transferred to naive mice with only 10(2) splenic T cells. Here we show that 10(2) T cell-depleted spleen cells (i.e., APCs) from orally tolerized donors can also transfer nickel tolerance. This cannot be explained by simple passive transfer of the tolerogen. The APCs from orally tolerized donors displayed a reduced allostimulatory capacity, a tolerogenic phenotype, and an increased expression of CD38 on B cells. In fact, it was B cells among the APCs that carried the thrust of tolerogenicity. Through serial adoptive transfers with Ly5.1(+) donors and two successive sets of Ly5.2(+) recipients, we demonstrated that nickel tolerance was infectiously spread from donor to host cells. After the transfer of either T cells or APCs from orally tolerized donors, the spread of tolerance to the opposite cell type of the recipients (i.e., APCs and T cells, respectively) required recipient immunization with NiCl(2)/H(2)O(2). For the spread of tolerance from a given donor cell type, T cell or APC, to the homologous host cell type, the respective opposite cell type in the host was required as intermediate. We conclude that T suppressor cells and tolerogenic APCs induced by oral administration of nickel are part of a positive feedback loop that can enhance and maintain tolerance when activated by Ag associated with a danger signal. Under these conditions, APCs and T suppressor effector cells infectiously spread the tolerance to naive T cells and APCs, respectively.
authors.affiliation: Institut für umweltmedizinische Forschung and Dermatology Clinic, Heinrich Heine University, Düsseldorf, Germany.
authors.forename: Karin
authors.initials: K
authors.lastname: Roelofs-Haarhuis
authors.forename: Xianzhu
authors.initials: X
authors.lastname: Wu
authors.forename: Michael
authors.initials: M
authors.lastname: Nowak
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.forename: Suzan
authors.initials: S
authors.lastname: Artik
authors.forename: Ernst
authors.initials: E
authors.lastname: Gleichmann
mesh_terms: D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D000938:Antigen-Presenting Cells / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D000950:Antigens, Ly / Q000096:biosynthesis; D016175:B-Lymphocyte Subsets / Q000276:immunology / Q000637:transplantation; D002450:Cell Communication / Q000276:immunology*; D002478:Cells, Cultured; D005260:Female; D006861:Hydrogen Peroxide / Q000008:administration & dosage / Q000276:immunology; D007108:Immune Tolerance; D007114:Immunization / Q000379:methods; D016130:Immunophenotyping; D007271:Injections, Intradermal; D007959:Lymphocyte Culture Test, Mixed; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D023421:Models, Animal; D009532:Nickel / Q000008:administration & dosage* / Q000276:immunology*; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism / Q000637:transplantation; D013997:Time Factors
chemical_list: D000950:Antigens, Ly; C022838:nickel chloride; D009532:Nickel; D006861:Hydrogen Peroxide