TitleExpression 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.
Publication TypeJournal Article
Year of Publication2009
AuthorsFunatake CJ, Ao K, Suzuki T, Murai H, Yamamoto M, Fujii-Kuriyama Y, Kerkvliet NI, Nohara K
JournalJ Immunotoxicol
Volume6
Issue3
Pagination194-203
Date Published2009 Sep
ISSN1547-6901
KeywordsAdministration, Oral, Adoptive Transfer, Animals, Cytotoxicity, Immunologic, Disease Models, Animal, Down-Regulation, Graft vs Host Disease, Hazardous Substances, Immunosuppression, Interleukin-2 Receptor alpha Subunit, Isoantigens, L-Selectin, Mice, Mice, Inbred C57BL, Mice, Knockout, Mice, Transgenic, Polychlorinated Dibenzodioxins, Receptors, Aryl Hydrocarbon, T-Lymphocytes, Cytotoxic, T-Lymphocytes, Regulatory
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(hi)CD62L(low) 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.

DOI10.1080/15476910903124454
Alternate JournalJ Immunotoxicol
PubMed ID19635034