|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|
|Date Published||2009 Sep|
|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|
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.
|Alternate Journal||J Immunotoxicol|