Antigen-specific CD8 T cells can eliminate antigen-bearing keratinocytes with clonogenic potential via an IFN-gamma-dependent mechanism.
The immune system surveys the skin for keratinocytes (KCs) infected by viruses or with acquired genetic damage. The mechanism by which T cells mediate KC elimination is however undefined. In this study we show that antigen-specific CD8 T cells can eliminate antigen-bearing KCs in vivo and inhibit their clonogenic potential in vitro, independently of the effector molecules perforin and Fas-ligand (Fas-L). In contrast, IFN-gamma receptor expression on KCs and T cells producing IFN-gamma are each necessary and sufficient for in vitro inhibition of KC clonogenic potential. Thus, antigen-specific cytotoxic T lymphocytes (CTLs) may mediate destruction of epithelium expressing non-self antigen by eliminating KCs with potential for self-renewal through an IFN-gamma-dependent mechanism.
The University of Queensland Diamantina Institute, Princess Alexandra Hospital, Brisbane, Queensland, Australia.
Rachel L
RL
De Kluyver
Linnea
L
Moritz
Craig A
CA
Harris
Hiroaki
H
Azukizawa
Ian H
IH
Frazer
D000818:Animals; D017209:Apoptosis / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D002450:Cell Communication / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D002460:Cell Line; D002999:Clone Cells / Q000166:cytology / Q000276:immunology; D053222:Fas Ligand Protein / Q000276:immunology; D005260:Female; D006084:Graft Rejection / Q000276:immunology; D007371:Interferon-gamma / Q000235:genetics* / Q000276:immunology*; D015603:Keratinocytes / Q000166:cytology / Q000276:immunology*; D008285:Major Histocompatibility Complex / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D052899:Pore Forming Cytotoxic Proteins / Q000276:immunology; D012867:Skin / Q000166:cytology* / Q000276:immunology*; D016038:Skin Transplantation / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D052899:Pore Forming Cytotoxic Proteins; C483886:perforin, mouse; D007371:Interferon-gamma