SEROTONIN-STIMULATED AORTIC ENDOTHELIAL-CELLS SECRETE A NOVEL T-LYMPHOCYTE CHEMOTACTIC AND GROWTH-FACTOR

Atherosclerotic lesions contain multiple cell types including smooth m uscle cells, macrophages, and T lymphocytes. The development of an ext ralymphatic T lymphocyte focus of inflammation in this condition requi res chemoattractant-induced cell migration and growth factor-induced c ell activation. In a previous study, we described a novel 13-15-kDa T lymphocyte-specific chemotactic cytokine, endothelial cell-derived lym phocyte chemoattractant activity (ED-LCA), secreted by serotonin-stimu lated bovine aortic endothelial cells that is distinct from previously identified endothelial cell-derived interleukins (IL) 1, 6, and 8. Be cause of the association between T lymphocyte chemotactic and growth f actor activity, in the current study we investigated the effect of ED- LCA on T cell growth. We assessed its capacity to induce markers of th e passage of T cells from the resting (G(o)) state into the G(1) phase of the cell cycle, such as receptors for IL-2 (IL-PR) and transferrin (TFR) and class II major histocompatibility complex antigens (HLA-DR) . Incubation of G(o) freshly isolated human T lymphocytes for 48 h wit h chromatographically resolved, partially purified ED-LCA resulted in a threefold increase in expression of the p55 subunit of IL-2R, a thre efold increase in TFR, and a twofold increase in HLA-DR. Passage into the G(1) phase of the cell cycle was confirmed by cell cycle analysis employing acridine orange. Evaluation of CD4(+) and CD8(+) T cell subs ets by double-antibody labeling demonstrated that the p55 subunit of I L-SR was induced in both T cell subsets. Although incubation of human T cells with ED-LCA alone did not induce proliferation, addition of ex ogenous IL-2 to T cells pulsed with ED-LCA for 24 h caused a prolifera tive response with a stimulation index of 3. By up-regulating function al cell surface receptors for IL-2, ED-LCA is a competence growth fact or for T lymphocytes and primes them to respond to IL-2. By virtue of its effect on T cells, as a chemotactic and competence factor, this en dothelial cell-derived mitoattractant could participate with other T c ell growth factors like IL-2 in the recruitment and amplification of t he extralymphatic T cell component of atherosclerosis.