Migration of blood-borne lymphocytes into lymphoid tissues is initiated by
the L-selectin and alpha 4 beta 7 integrin adhesion molecules. Previous stu
dies have shown that L-selectin adhesion is dynamically regulated by febril
e temperatures. It is now reported that fever-range hyperthermia also acts
directly on lymphocytes to enhance selected adhesive functions of alpha 4 b
eta 7 integrin. :Fever-range hyperthermia treatment in vitro (40 degrees C,
12 h) of murine TK1 lymphoma cells and human peripheral blood lymphocytes
(PBL) stimulates alpha 4 beta 7 integrin-dependent adhesion to high endothe
lial venules (HEV) in Peyer's patch and mesenteric lymph node frozen sectio
ns. TK1 cells are alpha 4 beta 7(hi) L-selectin(lo), allowing for the analy
sis of alpha 4 beta 7 integrin without contributions from L-selectin. Adhes
ion was further shown to involve alpha 4 beta 7 integrin and its endothelia
l counter-receptor, mucosal addressin cell adhesion molecule-1 (MAdCAM-1) u
sing function-blocking antibodies (i.e. DATK32, HP2/1, MECA-367). Fever-ran
ge hyperthermia also promotes alpha 4 beta 7 integrin-mediated aggregation
of TK1 cells, In sharp contrast, hyperthermia fails to increase alpha 4 bet
a 7 integrin adhesion to fibronectin by TK1 cells. Expression of the alpha
4 beta 7 heterodimer on TK1 cells or human PBL is not altered by hypertherm
ia, suggesting that hyperthermia stimulates adhesion by enhancing alpha 4 b
eta 7 integrin avidity rather than its cell surface density. These results
provide a mechanism whereby febrile temperatures during infection or clinic
al hyperthermia potentially amplify the immune response by stimulating L-se
lectin and alpha 4 beta 7 integrin-dependent homing of immune effector cell
s to lymphoid tissues.