The Journal of Experimental Medicine
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Published 1 April 2002. doi:10.1084/jem.20012000
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© Rockefeller University Press, 0022-1007/2002/4/855/ $5.00
The Journal of Experimental Medicine, Volume 195, Number 7, April 1, 2002 855-867

Original Article

 Resident Skin-specific {gamma}{delta} T Cells Provide Local, Nonredundant Regulation of Cutaneous Inflammation

Michael Girardi1, Julia Lewis1, Earl Glusac1, Renata B. Filler1, Liping Geng2, Adrian C. Hayday3 and Robert E. Tigelaar1,2

1 Department of Dermatology and the Yale Skin Diseases Research Core Center, Yale University, New Haven, CT 06520
2 Section of Immunobiology, Yale University, New Haven, CT 06520
3 Peter Gorer Department of Immunobiology, Guy's King's St. Thomas' School of Medicine, Guy's Hospital, London, United Kingdom SE1 9RT

Address correspondence to Robert E. Tigelaar, Yale University School of Medicine, P.O. Box 208059, 333 Cedar St., New Haven, CT 06520-8059. Phone: 203-785-4968; Fax: 203-785-7234; E-mail: robert.tigelaar{at}yale.edu

The function of the intraepithelial lymphocyte (IEL) network of T cell receptor (TCR) {gamma}{delta}+ (V{gamma}5+) dendritic epidermal T cells (DETC) was evaluated by examining several mouse strains genetically deficient in {gamma}{delta} T cells ({delta}-/- mice), and in {delta}-/- mice reconstituted with DETC or with different {gamma}{delta} 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.ß-/- {delta}-/- mice lacking all T cells, indicating that {alpha}ß T cell–mediated inflammation is the target for {gamma}{delta}-mediated down-regulation. Reconstitution studies demonstrated that both spontaneous and augmented irritant dermatitis in FVB.{delta}-/- mice were down-regulated by V{gamma}5+ DETC, but not by epidermal T cells expressing other {gamma}{delta} TCRs. This study demonstrates that functional impairment at an epithelial interface can be specifically attributed to absence of the local TCR-{gamma}{delta}+ IEL subset and suggests that systemic inflammatory reactions may more generally be subject to substantial regulation by local IELs.

Key Words: dermatitis • TCR {gamma}{delta} • mast cells • NOD • FVB


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