Activation of the aryl hydrocarbon receptor reduces the number of precursor and effector T cells, but preserves thymic CD4+CD25+Foxp3+ regulatory T cells

Aryl hydrocarbon receptor (AhR) activation suppresses immune responses, including allergic sensitization, by increasing the percentage of regulatory (Treg) cells. Furthermore, AhR activation is known to affect thymic precursor T cells. However, the effect of AhR activation on intrathymic CD4 + CD25 + Foxp3 + Treg cells is unknown. Therefore, we investigated the effect of AhR activation on the percentage and number of CD4 + CD25 + Foxp3 + Treg cells during allergic sensitization in relevant immunological organs. C3H/HeOuJ mice were treated on day 0 with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and subsequently sensitized to peanut. On day 8, mice were sacrificed and thymus, spleen and mesenteric lymph nodes (MLN) were isolated. TCDD treatment decreased the number of CD4 − CD8 − , CD4 + CD8 + , CD4 + CD8 − and CD4 − CD8 + precursor T cells, but not the number of thymic CD4 + CD25 + Foxp3 + Treg cells. TCDD treatment increased the number of splenic CD4 + CD25 + Foxp3 + Treg cells and decreased Th1, Th2 and cytotoxic T cells in the spleen. This appeared to be independent of allergic sensitization. In MLN, TCDD treatment suppressed the increase of the number of CD4 + CD25 + Foxp3 + Treg cells, Th1, Th2 and cytotoxic T cells induced by peanut sensitization. Together, TCDD treatment preserves thymic CD4 + CD25 + Foxp3 + Treg cells and decreases peripheral T helper and cytotoxic T cells. This effect of TCDD may contribute to the increased influence of CD4 + CD25 + Foxp3 + Treg cells on immune mediated responses and to the understanding of how AhR activation modulates immune mediated diseases, including food allergy.