Induction of transendothelial migration in normal and malignant human T lymphocytes.
Activated CD 3+ enriched human peripheral blood T cells exhibited potent capacity for transendothelial migration through HUVEC layers in the absence of T cell ***. In contrast, malignant human T cell lines *** no or negligible ability of transendothelial migration in the absence of chemoattractants. Time lapse studies of transendothelial migration of activated CD 3+ enriched peripheral blood T cells through a HUVEC layer showed that the first T cells were detected in the lower compartment of a tissue culture insert after 1 hour and that migration increased to reach a maximum of 25 x 10(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 that adhesion of T cells to HUVECs was primarily mediated by CD11a/CD18 and ICAM-1 interactions. Furthermore, transendothelial migration of CD 3+ enriched 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 migrated well on extracellular matrix components as determined by using Boyden chambers. Crosslinking of alpha 1 beta 2 and alpha 4 beta 1 with immobilized monoclonal antibodies induced motile behaviour in activated CD 3 enriched human peripheral blood T cells but not in malignant T cell lines. In conclusion, the differences in the ability of transendothelial migration between normal and malignant human T cells in the absence of chemoattractants is primarily due to the differences in the capacity of alpha 1 beta 2 and alpha 4 beta 1 to trigger motile behaviour in the separate cell types.
Hauzenberger
D
D
Laboratory of the Centre Pluridiscipllnaire d'Oncologie (CPO), Swiss Institute for Experimental Cancer Research (ISREC), Epalinges, Switzerland.
Hultenby
K
K
Sumitran
S
S
Ruegg
C
C
Klominek
J
J
D000328:Adult; D002448:Cell Adhesion; D002465:Cell Movement; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000166:cytology*; D016326:Extracellular Matrix Proteins / Q000502:physiology; D006801:Humans; D016023:Integrins / Q000032:analysis; D013601:T-Lymphocytes / Q000502:physiology*; D014407:Tumor Cells, Cultured
D016326:Extracellular Matrix Proteins; D016023:Integrins