Adhesion molecules expressed on homing lymphocytes in model intestinal epithelia.
OBJECTIVE
The development of intestinal intraepithelial lymphocytes (IELs) requires the movement of lymphocytes into the epithelial compartment (i.e., IEL homing). The rules governing and the biologic consequences of IEL homing are poorly understood. The aims of this study were to examine the adhesion molecules involved in IEL homing and the phenotypic alteration of lymphocytes as a consequence of homing.


METHODS
We previously developed an in vitro IEL homing model consisting of human IEL cell lines and a polarized monolayer of human intestinal epithelial T84 cells. Homing capacity of lymphocytes was assessed by measuring their migration into epithelial monolayers, and phenotypic analysis was performed by flow cytometry.


RESULTS
In this model, approximately 30% of lymphocytes moved into the epithelial monolayer, regardless of the lymphocyte concentration. Flow cytometric screening of adhesion molecules revealed that homed lymphocytes expressed high levels of integrin alphaXbeta2 and alphaEbeta7 and low levels of alpha4beta7 compared with non-homed lymphocytes. In addition, subpopulations sorted as alphaXbeta2(high) or alphaEbeta7(high) independently showed greater homing capacities. After homing, alphaEbeta7 and intercellular adhesion molecule 1 (ICAM-1) on homed lymphocytes were significantly up-regulated, which was consistent with their high expression observed on freshly isolated human IELs. The up-regulation of alphaEbeta7 (but not ICAM-1) was completely dependent on epithelial-derived transforming growth factor beta1 (TGF-beta1). The expression of alphaXbeta2 was observed on a small population of freshly isolated human IELs, and was markedly induced by stimulation. Also, epithelial-derived TGF-beta1 down-regulated the alphaXbeta2 expression (an event likely to occur after homing).


CONCLUSIONS
Our findings indicate a relationship between IEL alphaXbeta2 and alphaEbeta7 expression and homing into intestinal epithelia. We also show that phenotypic alteration of IELs is induced by close interaction with intestinal epithelia as a consequence of homing.
Shibahara
T
T
Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30322, USA. tshibah@emory.edu
Si-Tahar
M
M
Shaw
S K
SK
Madara
J L
JL
D002460:Cell Line; D002633:Chemotaxis; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D016167:Integrin alphaXbeta2; D016023:Integrins; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics; D007413:Intestinal Mucosa / Q000276:immunology*; D008213:Lymphocyte Activation; D008214:Lymphocytes / Q000276:immunology* / Q000502:physiology; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000235:genetics*; D016212:Transforming Growth Factor beta / Q000494:pharmacology
D016167:Integrin alphaXbeta2; D016023:Integrins; D008562:Membrane Glycoproteins; D016212:Transforming Growth Factor beta; C071777:integrin alpha4beta7; D018799:Intercellular Adhesion Molecule-1