Resident skin-specific gammadelta T cells provide local, nonredundant regulation of cutaneous inflammation

J Exp Med. 2002 Apr 1;195(7):855-67. doi: 10.1084/jem.20012000.

Abstract

The function of the intraepithelial lymphocyte (IEL) network of T cell receptor (TCR) gammadelta(+) (Vgamma5(+)) dendritic epidermal T cells (DETC) was evaluated by examining several mouse strains genetically deficient in gammadelta T cells (delta(-/-) mice), and in delta(-/-) mice reconstituted with DETC or with different gammadelta cell subpopulations. NOD.delta(-/-) and FVB.delta(-/-) mice spontaneously developed localized, chronic dermatitis, whereas interestingly, the commonly used C57BL/6.delta(-/-) strain did not. Genetic analyses indicated a single autosomal recessive gene controlled the dermatitis susceptibility of NOD.delta(-/-) mice. Furthermore, allergic and irritant contact dermatitis reactions were exaggerated in FVB.delta(-/-), but not in C57BL/6.delta(-/-) mice. Neither spontaneous nor augmented irritant dermatitis was observed in FVB.beta(-/-) delta(-/-) mice lacking all T cells, indicating that alphabeta T cell-mediated inflammation is the target for gammadelta-mediated down-regulation. Reconstitution studies demonstrated that both spontaneous and augmented irritant dermatitis in FVB.delta(-/-) mice were down-regulated by Vgamma5(+) DETC, but not by epidermal T cells expressing other gammadelta TCRs. This study demonstrates that functional impairment at an epithelial interface can be specifically attributed to absence of the local TCR-gammadelta(+) IEL subset and suggests that systemic inflammatory reactions may more generally be subject to substantial regulation by local IELs.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Dendritic Cells / immunology
  • Dermatitis / genetics
  • Dermatitis / immunology*
  • Dermatitis / pathology
  • Genes, Recessive
  • Genes, T-Cell Receptor delta*
  • Inflammation / immunology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Inbred ICR
  • Mice, Knockout
  • Receptors, Antigen, T-Cell, gamma-delta / deficiency
  • Receptors, Antigen, T-Cell, gamma-delta / genetics
  • Receptors, Antigen, T-Cell, gamma-delta / immunology*
  • Skin / immunology*
  • T-Lymphocytes / drug effects
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / pathology
  • Tetradecanoylphorbol Acetate / pharmacology

Substances

  • Receptors, Antigen, T-Cell, gamma-delta
  • Tetradecanoylphorbol Acetate