T Shibahara1, M Si-Tahar, S K Shaw, J L Madara. 1. Department of Pathology and Laboratory Medicine, Emory University, Atlanta, Georgia 30322, USA. tshibah@emory.edu
Abstract
BACKGROUND & AIMS: 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.
BACKGROUND & AIMS: 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.
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