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. |
Publication Type | Journal Article |
Year of Publication | 2009 |
Authors | Funatake CJ, Ao K, Suzuki T, Murai H, Yamamoto M, Fujii-Kuriyama Y, Kerkvliet NI, Nohara K |
Journal | J Immunotoxicol |
Volume | 6 |
Issue | 3 |
Pagination | 194-203 |
Date Published | 2009 Sep |
ISSN | 1547-6901 |
Keywords | Administration, 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. |
DOI | 10.1080/15476910903124454 |
Alternate Journal | J Immunotoxicol |
PubMed ID | 19635034 |