The Journal of Immunology, Vol 145, Issue 1 140-148, Copyright © 1990 by American Association of Immunologists

ARTICLES

Human T lymphocyte adhesion to endothelial cells and transendothelial migration. Alteration of receptor use relates to the activation status of both the T cell and the endothelial cell

N Oppenheimer-Marks, LS Davis and PE Lipsky
Harold C. Simmons Arthritis Research Center, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235.

An in vitro model of T cell adhesion to human umbilical vein endothelial cells (HUVEC) and transendothelial migration was used to determine whether the activation state of the T cell or cytokine exposure of the HUVEC altered T cell-HUVEC interactions or receptor utilization. Stimulation of T cells with the activator of protein kinase C, phorbol dibutyrate (PDB) alone or in combination with the calcium ionophore, ionomycin increased their binding to HUVEC. Much of the binding of control and activated T cells to HUVEC was mediated by leukocyte function-associated Ag-1 (LFA-1) (CD11a/CD18), because mAb to either chain of this molecule inhibited binding substantially, but not completely. Activation of HUVEC with IL-1 also increased binding of T cells. Binding of control T cells to IL-1-stimulated HUVEC, however, was found to be LFA-1 independent, because mAb to CD11a/CD18 failed to block the interaction. In contrast, binding of activated T cells to IL- 1-stimulated HUVEC was partially inhibited by mAb to LFA-1. Binding of activated T cells to IL-1-stimulated HUVEC also involved CD44 because this interaction was partially blocked by mAb to this determinant. When T cell migration was analyzed, it was found that the migration of PDB- activated T cells was three to four-fold more than that of control T cells. Migration through HUVEC and random migration were both enhanced by PDB stimulation. However, when the T cells were costimulated with PDB and ionomycin, migration was not increased above that of control T cells. PDB-activated T cells appeared to use LFA-1 for migration regardless of the activation status of the HUVEC, because mAb to CD11a/CD18 partially blocked their migration after binding to HUVEC. There was also a modest inhibition of PDB-activated T cell migration by mAb to CD44. In contrast, migration of control T cells involved neither LFA-1 nor CD44. Finally, binding of control T cells to high endothelial venules of peripheral lymphoid tissue was found to be CD11a/CD18 and CD44 independent, and completely inhibited by activation with either PDB or the combination of PDB and ionomycin. These results demonstrate that T cells use LFA-1 and CD44 as well as other as yet unidentified adhesion receptors for interactions with HUVEC, and that use of these adhesion receptors is mutable and related to the activation state of the T cell and cytokine stimulation of the HUVEC.

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