Induction of transendothelial migration in normal and malignant human T lymphocytes

Activated CD 3+ enriched human peripheral blood T cells exhibited potent ca pacity for transendothelial migration through HUVEC layers in the absence o f T cell chemoattrqactants. In contrast, malignant human T cell lines showe d no or negligible ability of transendothelial migration in the absence of chemoattractants. Time lapse studies of transendothelial migration of activ ated CD 3+ enriched peripheral blood T cells through a HUVEC layer showed t hat the first T cells were detected in the lower compartment of a tissue cu lture insert after 1 hour and that migration increased to reach a maximum o f 25x10(4) T cells/hr after 24 hours. Adhesion assays of human T cell lines demonstrated that all T cell lines were capable of adhesion to HUVEC and t hat adhesion of T cells to HUVECs was primarily mediated by CD11a/CD18 and ICAM-1 interactions. Furthermore, transendothelial migration of CD 3+ enric hed human peripheral blood T cells was inhibited by pretreating the T cells with anti-CD 18 monoclonal antibodies. The inability of malignant T cells to migrate through HUVEC layers in the absence of chemoattractants was not due to poor motility per se, since both normal and malignant T cells migrat ed well on extracellular matrix components as determined by using Boyden ch ambers. Crosslinking of alpha(L)beta(2) and alpha(4)beta(1) with immobilize d monoclonal antibodies induced motile behaviour in activated CD 3 enriched human peripheral blood T cells but not in malignant T cell lines. In concl usion, the differences in the ability of transendothelial migration between normal and malignant human T cells in the absence of chemoattractants is p rimarily due to the differences in the capacity of alpha(L)beta(2) and alph a(4)beta(1) to trigger motile behaviour in the separate cell types.