HUMAN ENDOTHELIAL-CELLS INDUCE AND REGULATE CYTOLYTIC T-CELL DIFFERENTIATION

We compared the capacity of cultured human endothelial cells (EC) vs B lymphoblastoid cells (BLC) from the same donor to stimulate allogenei c CD8(+) T cells to differentiate into CTL, assaying for allorestricte d cytotoxicity, T cell growth, IFN-gamma secretion, and perforin expre ssion. The input cell number affected specificity and potency of the r esulting CTL, At low input (<10(5) cells/well), anti-EC CTL were rarel y detected, At high input (>10(6) cells/well), anti-EC CTL developed t hat displayed unrestricted, low-titer killing and an unstable phenotyp e, 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 d id 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-B LC CTL was completely suppressed, while the anti-EC response was intac t. The inhibition of the allogeneic anti-BLC CTL response was independ ent of T cell-EC contact, and proliferation of CD8(+) T cells was inhi bited 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.