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

Castle J. Funatake, Kana Ao, Takehiro Suzuki, Hikari Murai, Masayuki Yamamoto, Yoshiaki Fujii-Kuriyama, Nancy I. Kerkvliet, Keiko Nohara

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)194-203
Number of pages10
JournalJournal of Immunotoxicology
Volume6
Issue number3
DOIs
Publication statusPublished - 2009

Keywords

  • AhR
  • CTL response
  • Regulatory T-cells
  • TCDD
  • Transgenic mouse

ASJC Scopus subject areas

  • Immunology
  • Toxicology

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