Sp. Colgan et al., INTERFERON-GAMMA INDUCES A CELL-SURFACE PHENOTYPE SWITCH ON T84 INTESTINAL EPITHELIAL-CELLS, The American journal of physiology, 267(2), 1994, pp. 30000402-30000410
Intestinal epithelia are in intimate contact with submucosal and intra
epithelial lymphocytes. The concentration of intraepithelial lymphocyt
es increases during inflammatory processes, and, when stimulated, thes
e cells generate cytokines such as interferon-gamma (IFN-gamma). In th
is study, we examined the effect of recombinant human IFN-gamma on ion
transport events in T84 cells, a crypt epithelial cell line widely us
ed to study electrogenic Cl- secretion, the transport event responsibl
e for mucosal hydration. Epithelial exposure to IFN-gamma brought abou
t a marked attenuation in stimulated Cl- secretion, as measured by gen
eration of short-circuit current (I-sc) This IFN-gamma-elicited decrea
se in the Cl- secretory response was present for a variety of specific
agonists, appeared largely due to IFN-gamma interactions with the bas
olateral surface, and did not result from a defect in second messenger
generation. Efflux and uptake studies were utilized to functionally d
efine the individual cell surface transport proteins that participate
in Cl- secretion and revealed that, in response to epithelial exposure
to IFN-gamma, apical Cl- channels and basolateral Na+-K+-2Cl(-) cotra
nsporters, K+ channels, and Na-K-adenosinetriphosphatase were all func
tionally downregulated. [H-3]bumetanide binding assays suggested that
surface expression of the cotransporter was diminished by >70% after I
FN-gamma preexposure. Concurrently, surface immunofluorescence studies
revealed that epithelial exposure to IFN-gamma brought about the indu
ction of major histocompatibility complex (MHC) class II molecule expr
ession on T84 epithelial monolayers and markedly increased MHC class I
surface expression. Finally, neutrophilepithelial adhesion studies re
vealed that preexposure of epithelial monolayers to IFN-gamma elicited
a beta(2)-integrin-dependent induction of neutrophil adhesion. These
results suggest a global ''phenotypic switch'' on the intestinal epith
elial cell surface from one exhibiting classical epithelial transport
function to one expressing significant immune accessory function.