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Blood, 1 May 2001, Vol. 97, No. 9, pp. 2727-2733
IMMUNOBIOLOGY
Fever-range hyperthermia dynamically regulates lymphocyte
delivery to high endothelial venules
Sharon S. Evans,
Wan-Chao Wang,
Mark D. Bain,
Randy Burd,
Julie R. Ostberg, and
Elizabeth A. Repasky
From the Department of Immunology, Roswell Park Cancer
Institute, Carlton and Elm Streets, Buffalo, NY.
Fever is associated with increased survival during acute
infection, although its mechanism of action is largely unknown. This study found evidence of an unexpectedly integrated mechanism by which
fever-range temperatures stimulate lymphocyte homing to secondary
lymphoid tissues by increasing L-selectin and  4 7
integrin-dependent adhesive interactions between circulating
lymphocytes and specialized high endothelial venules (HEV). Exposure of
splenic lymphocytes in vivo to fever-like whole-body hyperthermia (WBH;
39.8 ± 0.2°C for 6 hours) stimulated both L-selectin and
47 integrin-dependent adhesion of lymphocytes to HEV under shear
conditions in lymph nodes and Peyer patches. The adhesiveness of HEV
ligands for L-selectin and 47 integrin (ie, peripheral lymph node
addressin and mucosal addressin cell adhesion molecule-1) also
increased during WBH or febrile responses associated with
lipopolysaccharide-induced or turpentine-induced inflammation. Similar
increases in HEV adhesion occurred during hyperthermia treatment of
lymph node and Peyer patch organ cultures in vitro, indicating that the
local lymphoid tissue microenvironment is sufficient for the
hyperthermia response. In contrast, WBH did not augment adhesion in
squamous endothelium of nonlymphoid tissues. Analysis of homing of
47hi L-selectinlo murine TK1 cells and
L-selectinhi 47 integrin-negative 300.19/L-selectin
transfectant cells showed that fever-range temperatures caused a 3- to
4-fold increase in L-selectin and 47
integrin-dependent trafficking to secondary lymphoid tissues. Thus,
enhanced lymphocyte delivery to HEV by febrile temperatures
through bimodal regulation of lymphocyte and endothelial adhesion
provides a novel mechanism to promote immune surveillance.
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