Modulation of Langerhans cell phenotype, migration and maturation by agents known to cause herpes simplex virus reactivation in a mouse model.
The factors which control whether an asymptomatic or symptomatic infection in the skin follows reactivation of herpes simplex virus (HSV) in the sensory ganglia remain unclear. Xylene, retinoic acid and dimethylsuphoxide (DMSO) all stimulate similar levels of virus reactivation in the ganglia of latently infected mice, yet give rise to high, moderate and very low incidences of clinical skin disease, respectively. This observation suggests that the chemicals may be capable of affecting the local microenvironment of the skin. In the present study we have investigated the effects of xylene, retinoic acid and DMSO on Langerhans cell (LC) phenotype and function. The results show that none of the chemicals inhibit the phenotypic maturation of Langerhans cells in vitro. However, DMSO induced a dramatic elevation in class II MHC expression on Langerhans cells. In addition, fewer antigen-bearing dendritic cells (DC) were evident in the lymph nodes if xylene was administered to the skin prior to challenge with the contact sensitizer, FITC. None of the chemicals inhibited the accumulation of DC in the lymph nodes after such an antigen-challenge, suggesting that xylene was affecting not migration, but antigen uptake. The inhibition of antigen uptake by xylene together with the activation of LC in terms of class II expression by DMSO may explain, in part, the relative abilities of these chemicals to allow the establishment of recurrent HSV disease in the skin.
Manickasingham
S P
SP
Department of Pathology and Microbiology, University of Bristol, UK.
Hill
T J
TJ
Williams
N A
NA
D000818:Animals; D002465:Cell Movement / Q000187:drug effects; D002469:Cell Separation; D003713:Dendritic Cells / Q000378:metabolism; D004121:Dimethyl Sulfoxide / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000378:metabolism; D007801:Langerhans Cells / Q000187:drug effects / Q000502:physiology*; D008198:Lymph Nodes / Q000378:metabolism; D008297:Male; D051379:Mice; D010641:Phenotype; D018139:Simplexvirus / Q000254:growth & development*; D012867:Skin / Q000187:drug effects; D014212:Tretinoin / Q000494:pharmacology*; D014775:Virus Activation / Q000187:drug effects*; D014992:Xylenes / Q000494:pharmacology*
D000949:Histocompatibility Antigens Class II; D014992:Xylenes; D014212:Tretinoin; D004121:Dimethyl Sulfoxide