Induction of the chemokine receptor CXCR3 on TCR-stimulated T cells: dependence on the release from persistent TCR-triggering and requirement for IFN-gamma stimulation.
The chemokine receptor CXCR3 has been shown to play a key role in the recruitment of T cells to sites of inflammation such as allografts. Here, we investigated which signals and conditions areresponsible for CXCR3 induction. CXCR3 was induced on T cells that were stimulated with anti-CD3 plus anti-CD28 monoclonal antibodies and then recultured without any external stimuli. CXCR3 expression was inhibited when TCR stimulation was persistent in the reculture. CXCR3 induction also depended on the stimulation with IFN-gamma because CXCR3 expression was not induced in IFN-gamma-deficient T cells. The induction of another Th1 chemokine receptor CCR5 absolutely required IL-12 stimulation and STAT4 involvement. In contrast, CXCR3 was induced on STAT4-deficient T cells independently of IL-12 stimulation as long as IFN-gamma was produced as a result of potent TCR stimulation. These results show that CXCR3 induction on TCR-triggered T cells requires the release of these T cells from persistent TCR signaling and the stimulation with IFN-gamma and also indicate the differential regulatory mechanisms underlying the induction of two Th1 chemokine receptors.
Department of Oncology (C6), Osaka University Graduate School of Medicine, Osaka, Japan.
Chigusa
C
Nakajima
Takao
T
Mukai
Nobuya
N
Yamaguchi
Yasunari
Y
Morimoto
Woong-Ryeon
WR
Park
Masayuki
M
Iwasaki
Ping
P
Gao
Shiro
S
Ono
Hiromi
H
Fujiwara
Toshiyuki
T
Hamaoka
D000818:Animals; D004268:DNA-Binding Proteins / Q000502:physiology; D005260:Female; D007371:Interferon-gamma / Q000502:physiology*; D016753:Interleukin-10 / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D051379:Mice; D008807:Mice, Inbred BALB C; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D019713:Receptors, CCR5 / Q000096:biosynthesis; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000096:biosynthesis*; D050797:STAT4 Transcription Factor; D013601:T-Lymphocytes / Q000378:metabolism*; D015534:Trans-Activators / Q000502:physiology
C515188:Cxcr3 protein, mouse; D004268:DNA-Binding Proteins; D007376:Interleukin-2; D011948:Receptors, Antigen, T-Cell; D019713:Receptors, CCR5; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D050797:STAT4 Transcription Factor; C494091:Stat4 protein, mouse; D015534:Trans-Activators; D016753:Interleukin-10; D007371:Interferon-gamma