A keratinocyte-responsive gamma delta TCR is necessary for dendritic epidermal T cell activation by damaged keratinocytes and maintenance in the epidermis.
A unique population of T lymphocytes, designated dendritic epidermal T cells (DETC), homes to the murine epidermis during fetal development. DETC express a canonical gammadelta TCR, Vgamma3/Vdelta1, which recognizes Ag expressed on damaged, stressed, or transformed keratinocytes. Recently, DETC were shown to play a key role in the complex process of wound repair. To examine the role of the DETC TCR in DETC localization to the epidermis, maintenance in the skin, and activation in vivo, we analyzed DETC in the TCRdelta(-/-) mouse. Unlike previous reports in which the TCRdelta(-/-) skin was found to be devoid of any DETC, we discovered that TCRdelta(-/-) mice have alphabeta TCR-expressing DETC with a polyclonal Vbeta chain repertoire. The alphabeta DETC are not retained over the life of the animal, suggesting that the gammadelta TCR is critical for the maintenance of DETC in the skin. Although the alphabeta DETC can be activated in response to direct stimulation, they do not respond to keratinocyte damage. Our results suggest that a keratinocyte-responsive TCR is necessary for DETC activation in response to keratinocyte damage and for DETC maintenance in the epidermis.
Jameson
Julie M
JM
Department of Immunology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Cauvi
Gabrielle
G
Witherden
Deborah A
DA
Havran
Wendy L
WL
D000818:Animals; D002455:Cell Division / Q000235:genetics / Q000276:immunology; D002465:Cell Movement / Q000235:genetics / Q000276:immunology; D003713:Dendritic Cells / Q000276:immunology* / Q000378:metabolism; D004817:Epidermis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015333:Gene Rearrangement, beta-Chain T-Cell Antigen Receptor; D007111:Immunity, Cellular / Q000235:genetics; D016130:Immunophenotyping; D015603:Keratinocytes / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis / Q000235:genetics; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D016176:T-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D014945:Wound Healing / Q000235:genetics / Q000276:immunology*
D016693:Receptors, Antigen, T-Cell, alpha-beta; D016692:Receptors, Antigen, T-Cell, gamma-delta