Effects of TCDD on the fate of naive dendritic cells.
The environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), causes immune suppression via activation of the aryl hydrocarbon receptor. Dendritic cells (DCs), the professional antigen-presenting cells in the immune system, are adversely affected by TCDD. We hypothesized that TCDD alters DC homeostasis, resulting in a loss of DCs in naive mice. To test this hypothesis, C57Bl/6 mice were gavaged with either vehicle or an immunosuppressive dose of TCDD (15 microg/kg). TCDD exposure decreased the frequency and number of splenic CD11c(high) DCs on day 7 when compared with vehicle-treated controls. TCDD increased the expression of CD86 and CD54, while decreasing the frequency of splenic CD11c(high) DCs expressing CD11a and major histocompatibility complex (MHC) class II. Moreover, TCDD selectively decreased the CD11c(high)CD8alpha(-)33D1(+) splenic DCs specialized at activating CD4(+) T cells but did not affect the regulatory CD11c(high)CD8alpha(+)DEC205(+) splenic DCs. TCDD did not alter the number or frequency of CD11c(low) splenic DCs but decreased their MHC class II and CD11a expression. Loss of splenic CD11c(high) DCs was independent of Fas-mediated apoptosis and was not due to alterations in the numbers of common DC precursors in the bone marrow or their ability to generate steady-state DCs in vitro. Instead, increased CCR7 expression on CD11c(high) DCs suggested involvement of a migratory event. Popliteal and brachial lymph node CD11c(+) cells showed elevated levels of MHC class II and CD40 following TCDD exposure. Collectively, this study shows the presence of a TCDD-sensitive splenic DC subpopulation in naive mice, suggesting that TCDD may induce suppression of T-cell-mediated immunity by disrupting DC homeostasis.
Bankoti
Jaishree
J
Department of Biomedical and Pharmaceutical Sciences, University of Montana, Missoula, Montana 59812, USA.
Burnett
Andrea
A
Navarro
Severine
S
Miller
Andrea K
AK
Rase
Ben
B
Shepherd
David M
DM
D000284:Administration, Oral; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D001854:Bone Marrow Cells / Q000187:drug effects / Q000473:pathology; D002452:Cell Count; D003713:Dendritic Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004785:Environmental Pollutants / Q000633:toxicity*; D005260:Female; D008198:Lymph Nodes / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000633:toxicity*; D054400:Receptors, CCR7 / Q000378:metabolism; D013154:Spleen / Q000187:drug effects* / Q000473:pathology
D015703:Antigens, CD; C515371:Ccr7 protein, mouse; D004785:Environmental Pollutants; D000072317:Polychlorinated Dibenzodioxins; D054400:Receptors, CCR7