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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1995;15:1204-1210.)
© 1995 American Heart Association, Inc.

Articles

T Lymphocytes Affect Smooth Muscle Cell Phenotype and Proliferation

Barbara E. Rolfe; Julie H. Campbell; Nicole J. Smith; Merron W. Cheong; Gordon R. Campbell

From the Centre for Research in Vascular Biology, Department of Anatomical Sciences, University of Queensland, Queensland, Australia.

Correspondence to Dr J.H. Campbell, Centre for Research in Vascular Biology, Department of Anatomical Sciences, University of Queensland, Queensland 4072, Australia.

Abstract The effects of rabbit T lymphocytes on rabbit aortic smooth muscle cell (SMC) phenotype and proliferation were investigated in vitro. SMCs seeded at confluent density in primary culture had a volume fraction of myofilaments (V_vmyo) of 49.8±2.6% after 3 days of culture, not significantly different from that of freshly dispersed cells (V_vmyo, 54.1±2.1%). Sister cultures of SMCs to which Concanavalin A–activated T lymphocytes or T lymphocyte–conditioned medium was added had significantly lower V_vmyo (35.5±2.2% and 31.6±2.3%, respectively) at the same time point. We have previously shown that a decrease in V_vmyo could be induced by the heparan sulfate–degrading activity of living macrophages and by commercial preparations of heparinase. While activated T lymphocytes also completely degraded heparan sulfate–rich ³⁵S-labeled extracellular matrix (an effect inhibited by the addition of 10 µg/mL heparin), no heparanase-like activity was detected in T lymphocyte–conditioned medium, indicating that for this cell type SMC phenotypic change is induced by a different mechanism. Incubation of the T lymphocyte–derived cytokine interferon gamma (IFN-) with freshly isolated rat SMCs caused a significant reduction in V_vmyo at day 2 in primary culture from 54.3±2.1% (control) to 35.4±3.0%. Furthermore, a neutralizing antibody specific for IFN- removed the effect of T lymphocytes and medium conditioned by them, thus positively identifying IFN- as the T lymphocyte factor responsible for this activity. T lymphocyte–conditioned medium was mitogenic for passaged (low V_vmyo) SMCs. Although SMC proliferation was inhibited by exogenous IFN-, two other T lymphocyte products, granulocyte-macrophage–colony stimulating factor and tumor necrosis factor–ß, were found to stimulate proliferation, while interleukin-2 and interleukin-6 had no effect. It was concluded that T lymphocytes, by inducing SMC phenotypic change and stimulating proliferation, may play an important role in atherogenesis.

Key Words: smooth muscle cells • T lymphocytes • cytokines • phenotypic change • proliferation

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