Jr. Ostberg et al., Regulation of immune activity by mild (fever-range) whole body hyperthermia: effects on epidermal Langerhans cells, CELL STR CH, 5(5), 2000, pp. 458-461
Inflammation of the skin and systemic fever, both of which occur with injur
y or infection, include a hyperthermic component that many believe constitu
tes a physiological stress. Such increases in local or systemic body temper
ature may also have a regulatory effect on immune function. Langerhans cell
s (LCs), the dendritic cells of the skin, continuously monitor the extracel
lular matrix of the skin by taking up particles and microbes that they then
carry to draining lymph nodes for presentation to T lymphocytes. We hypoth
esize that the thermal element of inflammation and/or fever may help regula
te the activation and migration of LCs out of the epidermis. To test this h
ypothesis, Balb/ c mice were exposed to a mild (39.8 degreesC +/- 0.2 degre
esC), long-duration (6 hours) whole body hyperthermia (WBH) treatment, whic
h mimics the thermal component of fever. The number of LCs and their morpho
logy were analyzed at various time points up to 7 days after the initiation
of WBH. The LCs of the ear epidermis were visualized using a fluorescein i
sothiocyanate-conjugated antibody specific for the major histocompatibility
complex (MHC) class II molecule and confocal microscopy. Although MHC clas
s II staining was diffuse on the surface of the LC body and dendritic exten
sions of both WBH and control samples, the WBH-treated LCs exhibited a more
punctate morphology with fewer dendritic processes compared with control L
Cs. A significant decrease in the number of LCs was also observed 1 to 5 da
ys after WBH treatment. Furthermore, in vitro heating of Balb/c ear skin cu
ltures at 40 degreesC for 6 to 8 hours enhanced the numbers of viable LCs t
hat migrated into the culture wells. These results suggest that WBH treatme
nt stimulates epidermal LCs in the absence of foreign antigen.