title: Low zone tolerance requires ICAM-1 expression to limit contact hypersensitivity elicitation.
abstract: Painting subsensitizing doses of contact sensitizers on skin (low-dose tolerization) induces antigen (Ag)-specific tolerance, known as low zone tolerance (LZT), which has been experimentally demonstrated by the inhibition of contact hypersensitivity (CHS). Although LZT resulted from the inhibition of the sensitization phase, the effects on the effector/elicitation phase remain unknown. L-selectin and ICAM-1 regulate leukocyte influx into inflamed tissues during the elicitation phase of CHS. LZT was investigated in mice lacking either L-selectin or ICAM-1 to evaluate the roles these leukocyte receptors play in LZT during the elicitation phase. Low-dose tolerization effectively suppressed CHS in wild-type and L-selectin-deficient mice, but not in ICAM-1-deficient mice. Low-dose-tolerized ICAM-1-deficient splenocytes effectively suppressed the elicitation phase in naive wild-type recipients. Sensitized ICAM-1-deficient splenocytes showed normal proliferative responses to the sensitizing Ag and generated normal CHS in wild-type recipients. Thus, ICAM-1 deficiency did not affect sensitization. LZT was associated with a lack of ICAM-1 upregulation after elicitation, suggesting a potentially mechanistic role for ICAM-1. The blockade of IL-10, a possible mediator of LZT, produced by hapten-specific suppressor cells, abrogated LZT and restored ICAM-1 upregulation. These results indicate that low-dose tolerization controls CHS by abrogating ICAM-1 upregulation during the elicitation phase.
authors.affiliation: Department of Dermatology, Nagasaki University Graduate School of Biomedical Sciences, Sakamoto, Nagasaki, Japan.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Komura
authors.forename: Yohei
authors.initials: Y
authors.lastname: Iwata
authors.forename: Fumihide
authors.initials: F
authors.lastname: Ogawa
authors.forename: Ayumi
authors.initials: A
authors.lastname: Yoshizaki
authors.forename: Toshifumi
authors.initials: T
authors.lastname: Yamaoka
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Akiyama
authors.forename: Toshihide
authors.initials: T
authors.lastname: Hara
authors.forename: Minoru
authors.initials: M
authors.lastname: Hasegawa
authors.forename: Manabu
authors.initials: M
authors.lastname: Fujimoto
authors.forename: Shinichi
authors.initials: S
authors.lastname: Sato
mesh_terms: D019264:Adoptive Transfer; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D003877:Dermatitis, Contact / Q000276:immunology*; D007108:Immune Tolerance / Q000276:immunology*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics* / Q000276:immunology*; D016753:Interleukin-10 / Q000276:immunology; D019041:L-Selectin / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D013154:Spleen / Q000166:cytology / Q000276:immunology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000911:Antibodies, Monoclonal; D018799:Intercellular Adhesion Molecule-1; D019041:L-Selectin; D016753:Interleukin-10