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

• Published in: The Journal of experimental medicine Vol. 195; no. 7; p. 855
• Main Authors: Girardi, Michael, Lewis, Julia, Glusac, Earl, Filler, Renata B, Geng, Liping, Hayday, Adrian C, Tigelaar, Robert E
• Format: Journal Article
• Language: English
• Published: United States 01.04.2002
• Subjects: 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
• ISSN: 0022-1007
• DOI: 10.1084/jem.20012000

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.