Th1 and type 1 cytotoxic T cells dominate responses in T-bet overexpression transgenic mice that develop contact dermatitis.
Contact dermatitis in humans and contact hypersensitivity (CHS) in animal models are delayed-type hypersensitivity reactions mediated by hapten-specific T cells. Recently, it has become clear that both CD4(+) Th1 and CD8(+) type 1 cytotoxic T (Tc1) cells can act as effectors in CHS reactions. T-bet has been demonstrated to play an important role in Th1 and Tc1 cell differentiation, but little is known about its contribution to CHS. In the present study, we used C57BL/6 mice transgenic (Tg) for T-bet to address this issue. These Tg mice, which overexpressed T-bet in their T lymphocytes, developed dermatitis characterized by swollen, flaky, and scaly skin in regions without body hair. Skin histology showed epidermal hyperkeratosis, neutrophil, and lymphocyte infiltration similar to that seen in contact dermatitis. T-bet overexpression in Tg mice led to elevated Th1 Ig (IgG2a) and decreased Th2 Ig (IgG1) production. Intracellular cytokine analyses demonstrated that IFN-gamma was increased in both Th1 and Tc1 cells. Furthermore, Tg mice had hypersensitive responses to 2,4-dinitrofluorobenzene, which is used for CHS induction. These results suggest that the level of expression of T-bet might play an important role in the development of contact dermatitis and that these Tg mice should be a useful model for contact dermatitis.
Ishizaki
Kazusa
K
Department of Anatomy and Embryology, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Ibaraki, Japan. satoruta@md.tsukuba.ac.jp
Yamada
Akiko
A
Yoh
Keigyou
K
Nakano
Takako
T
Shimohata
Homare
H
Maeda
Atsuko
A
Fujioka
Yuki
Y
Morito
Naoki
N
Kawachi
Yasuhiro
Y
Shibuya
Kazuko
K
Otsuka
Fujio
F
Shibuya
Akira
A
Takahashi
Satoru
S
D000818:Animals; D017449:Dermatitis, Allergic Contact / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D003877:Dermatitis, Contact; D006968:Hypersensitivity, Delayed / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D007074:Immunoglobulin G / Q000097:blood; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D051379:Mice; D008822:Mice, Transgenic; D020825:T-Box Domain Proteins / Q000235:genetics / Q000502:physiology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D018417:Th1 Cells / Q000276:immunology*; D015533:Transcriptional Activation; D000098815:T-bet Transcription Factor
D007074:Immunoglobulin G; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; D007371:Interferon-gamma