T lymphocytes affect smooth muscle cell phenotype and proliferation.
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 (Vvmyo) of 49.8 +/- 2.6% after 3 days of culture, not significantly different from that of freshly dispersed cells (Vvmyo, 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 Vvmyo (35.5 +/- 2.2% and 31.6 +/- 2.3%, respectively) at the same time point. We have previously shown that a decrease in Vvmyo 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 micrograms/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-gamma) with freshly isolated rat SMCs caused a significant reduction in Vvmyo at day 2 in primary culture from 54.3 +/- 2.1% (control) to 35.4 +/- 3.0%. Furthermore, a neutralizing antibody specific for IFN-gamma removed the effect of T lymphocytes and medium conditioned by them, thus positively identifying IFN-gamma as the T lymphocyte factor responsible for this activity. T lymphocyte-conditioned medium was mitogenic for passaged (low Vvmyo) SMCs.(ABSTRACT TRUNCATED AT 250 WORDS)
Rolfe
B E
BE
Department of Anatomical Sciences, University of Queensland, Australia.
Campbell
J H
JH
Smith
N J
NJ
Cheong
M W
MW
Campbell
G R
GR
D000818:Animals; D001485:Basement Membrane / Q000378:metabolism; D002455:Cell Division; D002478:Cells, Cultured; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D066298:In Vitro Techniques; D007371:Interferon-gamma / Q000502:physiology; D008213:Lymphocyte Activation; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D011509:Proteoglycans / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D013601:T-Lymphocytes / Q000502:physiology*
D011509:Proteoglycans; D007371:Interferon-gamma; D016178:Granulocyte-Macrophage Colony-Stimulating Factor