title: 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.
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.
authors.affiliation: Environmental Health Sciences Division, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.
authors.forename: Castle J
authors.initials: CJ
authors.lastname: Funatake
authors.forename: Kana
authors.initials: K
authors.lastname: Ao
authors.forename: Takehiro
authors.initials: T
authors.lastname: Suzuki
authors.forename: Hikari
authors.initials: H
authors.lastname: Murai
authors.forename: Masayuki
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Fujii-Kuriyama
authors.forename: Nancy I
authors.initials: NI
authors.lastname: Kerkvliet
authors.forename: Keiko
authors.initials: K
authors.lastname: Nohara
mesh_terms: D000284:Administration, Oral; D019264:Adoptive Transfer; D000818:Animals; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000276:immunology; D006086:Graft vs Host Disease / Q000235:genetics / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D015386:Hazardous Substances / Q000008:administration & dosage / Q000633:toxicity; D007165:Immunosuppression Therapy; D053645:Interleukin-2 Receptor alpha Subunit / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D007519:Isoantigens / Q000276:immunology*; D019041:L-Selectin / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D000072317:Polychlorinated Dibenzodioxins / Q000008:administration & dosage / Q000633:toxicity; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D013602:T-Lymphocytes, Cytotoxic / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D050378:T-Lymphocytes, Regulatory / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology
chemical_list: D015386:Hazardous Substances; D053645:Interleukin-2 Receptor alpha Subunit; D007519:Isoantigens; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D019041:L-Selectin