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Vascular cell adhesion molecule-1 is expressed by cortical thymic
epithelial cells and mediates thymocyte adhesion. Implications for the
function of alpha4beta1 (VLA4) integrin in T-cell development
DR Salomon, L Crisa, CF Mojcik, JK Ishii, G Klier and EM Shevach
Department of Molecular and Experimental Medicine, The Scripps Research
Institute, La Jolla, CA 92037, USA.
T-cell development requires a series of discrete selection and activation
signals delivered to maturing progenitors in the thymic cortex and medulla.
We have previously shown the constitutive activity of the integrin,
alpha4beta1 (VLA4), on a unique subpopulation of immature cortical
thymocytes and proposed a role for integrin-mediated adhesion in positive
selection by cortical epithelium. In the present report we show that thymic
epithelial cell lines express vascular cell adhesion molecule-1 (VCAM-1) a
high-affinity ligand for apha4beta1, and that VCAM-1 mediates thymocyte
binding to these lines. Immunohistochemistry and confocal microscopy show
that VCAM-1 is selectively expressed in situ by thymic epithelium in the
cortex and corticomedullary junction, two locations at which VCAM-1 could
determine the interaction between immature thymocytes and selecting
elements on epithelial cells. In parallel, we confirmed that fibronectin
(FN), the alternative ligand for alpha4beta1, is expressed predominantly in
the medulla. These results suggest that VCAM-1 is an adhesive ligand in the
thymic cortex for the activated form of alpha4beta1 constitutively
expressed during development by immature double positive thymocytes. The
structural segregation of the alternative ligand, FN, to the medulla
suggests that medullary FN may regulate the migration, development, and
export of more mature thymocytes.
Volume 89,
Issue 7,
pp. 2461-2471,
04/01/1997
Copyright © 1997 by The American Society of Hematology
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