title: Human endothelial cells induce and regulate cytolytic T cell differentiation.
abstract: We compared the capacity of cultured human endothelial cells (EC) vs B lymphoblastoid cells (BLC) from the same donor to stimulate allogeneic CD8+ T cells to differentiate into CTL, assaying for allorestricted cytotoxicity, T cell growth, IFN-gamma secretion, and perforin expression. The input cell number affected specificity and potency of the resulting CTL. At low input (<10(5) cells/ well), anti-EC CTL were rarely detected. At high input (>10(6) cells/well), anti-EC CTL developed that displayed unrestricted, low-titer killing and an unstable phenotype. At intermediate input (1.0-2.5 x 10(5) cells/well), classical class I MHC-restricted, CD8+, and perforin-positive anti-EC CTL developed with reproducible frequencies. However, under all conditions EC were less efficient stimulators than BLC from the same donor. Anti-EC CTL did not kill BLC, whereas anti-BLC CTL killed BLC and EC from the same donor with comparable efficiency. When CD8+ T lymphocytes were grown in the presence of EC and BLC together, the differentiation of anti-BLC CTL was completely suppressed, while the anti-EC response was intact. The inhibition of the allogeneic anti-BLC CTL response was independent of T cell-EC contact, and proliferation of CD8+ T cells was inhibited by EC-conditioned medium. We conclude that EC are competent but less efficient activators of CTL differentiation than are BLC and that EC actively regulate differentiation and/or expansion of allospecific CTL.
authors.affiliation: Program in Molecular Cardiobiology, Boyer Center for Molecular Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
authors.forename: B C
authors.initials: BC
authors.lastname: Biedermann
authors.forename: J S
authors.initials: JS
authors.lastname: Pober
mesh_terms: D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D002450:Cell Communication; D002454:Cell Differentiation; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology*; D005312:Fetal Blood / Q000166:cytology; D006801:Humans; D007231:Infant, Newborn; D007371:Interferon-gamma / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D054353:Perforin; D052899:Pore Forming Cytotoxic Proteins; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology* / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
chemical_list: D008562:Membrane Glycoproteins; D052899:Pore Forming Cytotoxic Proteins; D054353:Perforin; D007371:Interferon-gamma