A constitutively active arylhydrocarbon receptor induces growth inhibition of jurkat T cells through changes in the expression of genes related to apoptosis and cell cycle arrest.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known to suppress T cell-dependent immune reactions through the activation of the arylhydrocarbon receptor (AhR). Our previous findings suggest that TCDD inhibits the activation and subsequent expansion of T cells following antigen stimulation in mice, leading to a decreased level of T cell-derived cytokines involved in antibody production. In the present study, we investigated the effects of activated AhR on T cells by transiently expressing a constitutively active AhR (CA-AhR) mutant in AhR-null Jurkat T cells. In agreement with our previous findings, CA-AhR markedly inhibited the growth of Jurkat T cells. The inhibited cell growth was found to be concomitant with both an increase in the annexin V-positive apoptotic cells and the accumulation of cells in the G(1) phase. The growth inhibition was also shown to be mediated by both xenobiotic response element (XRE)-dependent and -independent mechanisms, because an A78D mutant of the CA-AhR, which lacks the ability of XRE-dependent transcription, partially inhibited the growth of Jurkat T cells. Furthermore, we demonstrated that CA-AhR induces expression changes in genes related to apoptosis and cell cycle arrest. These expression changes were shown to be solely mediated in an XRE-dependent manner, because the A78D mutant of the CA-AhR did not induce them. To summarize, these results suggest that AhR activation causes apoptosis and cell cycle arrest, especially through expression changes in genes related to apoptosis and cell cycle arrest by the XRE-dependent mechanism, leading to the inhibition of T cell growth.
Ito
Tomohiro
T
Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.
Tsukumo
Shin-Ichi
S
Suzuki
Norio
N
Motohashi
Hozumi
H
Yamamoto
Masayuki
M
Fujii-Kuriyama
Yoshiaki
Y
Mimura
Junsei
J
Lin
Tien-Min
TM
Peterson
Richard E
RE
Tohyama
Chiharu
C
Nohara
Keiko
K
D017209:Apoptosis; D002453:Cell Cycle; D002455:Cell Division; D005786:Gene Expression Regulation; D006801:Humans; D019169:Jurkat Cells; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000502:physiology*; D020218:Response Elements / Q000502:physiology; D013601:T-Lymphocytes / Q000502:physiology*
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon