The differential role of L-selectin and ICAM-1 in Th1-type and Th2-type contact hypersensitivity

J Invest Dermatol. 2010 Jun;130(6):1558-70. doi: 10.1038/jid.2010.25. Epub 2010 Feb 25.

Abstract

Sensitization and challenge using DNFB induce contact hypersensitivity (CHS) with predominant type 1 helper (Th1) cell infiltration, whereas those using FITC generate CHS with Th2 cell infiltration. CHS results from inflammatory cell infiltration, a process that is highly regulated by the expression of multiple adhesion molecules. We attempted to determine the role of L-selectin and ICAM-1 in Th1- and Th2-type CHS induced by DNFB or FITC in mice lacking either L-selectin, ICAM-1, or both. Th1-type CHS induced by DNFB was inhibited by L-selectin and/or ICAM-1 deficiency, which was associated with reduced IFN-gamma expression. Similarly, Th2-type CHS induced by FITC was inhibited by L-selectin deficiency. However, Th2-type CHS was increased by ICAM-1 deficiency and accompanied by increased Th2 cytokine expression. Infiltration of in vitro-generated Th1 cells into the FITC-challenged skin decreased in ICAM-1-deficient mice, whereas in vitro-generated Th2 cell infiltration increased, suggesting that ICAM-1 mediates Th1 cell migration and that in the absence of ICAM-1, Th1 cell recruitment decreased, whereas relative Th2 cell migration increased. These results suggest that ICAM-1 mediates Th1 cell recruitment irrespective of DNFB or FITC and that L-selectin recruits Th1 cells in Th1-type CHS, whereas it recruits Th2 cells in Th2-type CHS.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Anti-Idiotypic / pharmacology
  • Cell Movement / physiology
  • Cells, Cultured
  • Cytokines / metabolism
  • Dermatitis, Contact / metabolism
  • Dermatitis, Contact / pathology
  • Dermatitis, Contact / physiopathology*
  • Dinitrofluorobenzene / adverse effects
  • Disease Models, Animal
  • Fluorescein-5-isothiocyanate / adverse effects
  • Haptens / pharmacology
  • Immunoglobulin E / metabolism
  • Intercellular Adhesion Molecule-1 / genetics
  • Intercellular Adhesion Molecule-1 / immunology
  • Intercellular Adhesion Molecule-1 / physiology*
  • Interferon-gamma / metabolism
  • L-Selectin / genetics
  • L-Selectin / immunology
  • L-Selectin / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Th1 Cells / pathology
  • Th1 Cells / physiology*
  • Th2 Cells / pathology
  • Th2 Cells / physiology*

Substances

  • Antibodies, Anti-Idiotypic
  • Cytokines
  • Haptens
  • Intercellular Adhesion Molecule-1
  • L-Selectin
  • Immunoglobulin E
  • Interferon-gamma
  • Dinitrofluorobenzene
  • Fluorescein-5-isothiocyanate