EVIDENCE THAT TGF-BETA CAN INHIBIT HUMAN T-LYMPHOCYTE PROLIFERATION THROUGH PARACRINE AND AUTOCRINE MECHANISMS

被引:62
作者
FOX, FE [1 ]
FORD, HC [1 ]
DOUGLAS, R [1 ]
CHERIAN, S [1 ]
NOWELL, PC [1 ]
机构
[1] UNIV PENN, SCH MED, DEPT PATHOL & LAB MED, PHILADELPHIA, PA 19104 USA
关键词
D O I
10.1006/cimm.1993.1177
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Transforming growth factor-β (TGF-β) has been documented as having an inhibitory effect on the proliferation and growth of human T-lymphocytes. We examined the relative contribution of both exogenous and endogenous TGF-β to this inhibitory action. Purified human peripheral blood T-cells were cultured with Con A (0.2 μg/ml), washed with methyl mannopyranoside, and then cultured in rIL-2 (5 U/ml) with or without TGF-β (80 pM). Proliferation, as measured by uptake of tritiated thymidine at 72 hr, was inhibited by added active TGF-β. Addition of neutralizing anti-TGF-β antibodies at the initiation of culture abrogated the antiproliferative effects of TGF-β. A mink lung cell bioassay was used to measure endogenous TGF-β production by the T-cells following transient acidification of the supernatants to activate latent TGF-β. T-lymphocytes cultured with rIL-2 alone produced low levels of TGF-β, first detectable at 72 hr. The addition of (active) TGF-β to these cultures resulted in earlier and higher levels of endogenously produced latent TGF-β protein. This was reflected at the mRNA level as well. The exogenously added active TGF-β appeared to be depleted during the culture period, presumably by the activated T-cells, which exhibited elevated levels of types I, II, and Ill TGF-β receptors. The increase in TGF-β protein levels was due to endogenous TGF-β synthesis and secretion as supported by a capture assay using 35 S-labeled culture supernatants. These findings indicate that both paracrine and autocrine mechanisms are involved in the inhibitory effects of TGF-β on the proliferation of normal human T-lymphocytes and suggest that other TGF-β-producing cells can augment production of TGF-β by activated T-lymphocytes. © 1993 Academic Press. All rights reserved.
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页码:45 / 58
页数:14
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