TY - JOUR
T1 - Expression of constitutively-active aryl hydrocarbon receptor in T-cells enhances the down-regulation of CD62L, but does not alter expression of CD25 or suppress the allogeneic CTL response
AU - Funatake, Castle J.
AU - Ao, Kana
AU - Suzuki, Takehiro
AU - Murai, Hikari
AU - Yamamoto, Masayuki
AU - Fujii-Kuriyama, Yoshiaki
AU - Kerkvliet, Nancy I.
AU - Nohara, Keiko
PY - 2009
Y1 - 2009
N2 - Activation of aryl hydrocarbon receptor (AhR) by 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) in T-cells is required for TCDD-induced suppression of the allogeneic CTL response and for induction of CD25 hiCD62Llow adaptive regulatory T-cells. Here, the ability of a constitutively-active AhR (CA-AhR) expressed in T-cells alone to replicate the effects of TCDD was examined. The response of CA-AhR-expressing B6 donor T-cells in B6xD2F1 mice was compared to the response of wild-type B6 donor T-cells in B6xD2F1 mice given a single dose of TCDD. Expression of CA-AhR in donor T-cells enhanced the down-regulation of CD62L on Day 2 after injection, similar to a single oral dose of TCDD, but did not induce up-regulation of CD25 on Day 2 or affect CTL activity on Day 10. This suggests that activation of AhR in T-cells alone may not be sufficient to alter T-cell responses in this acute graft-versus-host (GvH) model. Since host APC are responsible for activating the donor T-cells, we examined the influence of the F1 host's AhR on donor T-cell responses by creating an AhR-/- B6xD2F1 host that had a greatly diminished AhR response to TCDD compared to wild-type F1 mice. As in AhR / B6xD2F1 mice, the CTL response in AhR-/- B6xD2F1 mice was completely suppressed by TCDD. This suggests that either CA-AhR dose not fully replicate the function of TCDD-activated AhR in suppression of the CTL response, or that minimal activation of AhR in host cells is required to combine with activation of AhR in T-cells to elicit the immunosuppressive effects of TCDD.
AB - Activation of aryl hydrocarbon receptor (AhR) by 2,3,7,8- tetrachlorodibenzo-p-dioxin (TCDD) in T-cells is required for TCDD-induced suppression of the allogeneic CTL response and for induction of CD25 hiCD62Llow adaptive regulatory T-cells. Here, the ability of a constitutively-active AhR (CA-AhR) expressed in T-cells alone to replicate the effects of TCDD was examined. The response of CA-AhR-expressing B6 donor T-cells in B6xD2F1 mice was compared to the response of wild-type B6 donor T-cells in B6xD2F1 mice given a single dose of TCDD. Expression of CA-AhR in donor T-cells enhanced the down-regulation of CD62L on Day 2 after injection, similar to a single oral dose of TCDD, but did not induce up-regulation of CD25 on Day 2 or affect CTL activity on Day 10. This suggests that activation of AhR in T-cells alone may not be sufficient to alter T-cell responses in this acute graft-versus-host (GvH) model. Since host APC are responsible for activating the donor T-cells, we examined the influence of the F1 host's AhR on donor T-cell responses by creating an AhR-/- B6xD2F1 host that had a greatly diminished AhR response to TCDD compared to wild-type F1 mice. As in AhR / B6xD2F1 mice, the CTL response in AhR-/- B6xD2F1 mice was completely suppressed by TCDD. This suggests that either CA-AhR dose not fully replicate the function of TCDD-activated AhR in suppression of the CTL response, or that minimal activation of AhR in host cells is required to combine with activation of AhR in T-cells to elicit the immunosuppressive effects of TCDD.
KW - AhR
KW - CTL response
KW - Regulatory T-cells
KW - TCDD
KW - Transgenic mouse
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U2 - 10.1080/15476910903124454
DO - 10.1080/15476910903124454
M3 - Article
C2 - 19635034
AN - SCOPUS:70350459474
VL - 6
SP - 194
EP - 203
JO - Journal of Immunotoxicology
JF - Journal of Immunotoxicology
SN - 1547-691X
IS - 3
ER -