Aryl hydrocarbon receptor activation impairs the priming but not the recall of influenza virus-specific CD8+ T cells in the lung.
The response of CD8+ T cells to influenza virus is very sensitive to modulation by aryl hydrocarbon receptor (AhR) agonists; however, the mechanism underlying AhR-mediated alterations in CD8+ T cell function remains unclear. Moreover, very little is known regarding how AhR activation affects anamnestic CD8+ T cell responses. In this study, we analyzed how AhR activation by the pollutant 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) alters the in vivo distribution and frequency of CD8+ T cells specific for three different influenza A virus epitopes during and after the resolution of a primary infection. We then determined the effects of TCDD on the expansion of virus-specific memory CD8+ T cells during recall challenge. Adoptive transfer of AhR-null CD8+ T cells into congenic AhR(+/+) recipients, and the generation of CD45.2AhR(-/-)-->CD45.1AhR(+/+) chimeric mice demonstrate that AhR-regulated events within hemopoietic cells, but not directly within CD8+ T cells, underlie suppressed expansion of virus-specific CD8+ T cells during primary infection. Using a dual-adoptive transfer approach, we directly compared the responsiveness of virus-specific memory CD8+ T cells created in the presence or absence of TCDD, which revealed that despite profound suppression of the primary response to influenza virus, the recall response of virus-specific CD8+ T cells that form in the presence of TCDD is only mildly impaired. Thus, the delayed kinetics of the recall response in TCDD-treated mice reflects the fact that there are fewer memory cells at the time of reinfection rather than an inherent defect in the responsive capacity of virus-specific memory CD8+ cells.
Lawrence
B Paige
BP
Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, Pullman, WA 99164, USA. paige_lawrence@urmc.rochester.edu
Roberts
Alan D
AD
Neumiller
Joshua J
JJ
Cundiff
Jennifer A
JA
Woodland
David L
DL
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D045142:Cross-Priming; D004785:Environmental Pollutants / Q000494:pharmacology; D018984:Epitopes, T-Lymphocyte / Q000276:immunology*; D005260:Female; D007156:Immunologic Memory / Q000187:drug effects; D009980:Influenza A virus; D008168:Lung / Q000276:immunology / Q000821:virology*; D008213:Lymphocyte Activation; D051379:Mice; D008817:Mice, Mutant Strains; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D000072317:Polychlorinated Dibenzodioxins / Q000494:pharmacology; D018336:Receptors, Aryl Hydrocarbon / Q000819:agonists* / Q000235:genetics
D004785:Environmental Pollutants; D018984:Epitopes, T-Lymphocyte; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon