Differential effect of transforming growth factor-β1 on the activation of human naive and memory CD4+ T lymphocytes

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Abstract
Transforming growth factor-β1 (TGF-β1) can have stimulatory or inhibitory effects on cell growth. For several cell types, the effect of TGF-β1 was found to correlate with the differentiation stage of the cells and the presence of other cytoklnes. We have studied here the influence of TGF-β1 on CD4+ T cell activation in relation to the differentiation stage of the cells by evaluating the effect of TGF-β1 on the prollferatlve responses of purified CD4+CD45RA+ (unprfmed) and CD4+CD45RO+ (primed) lymphocytes. Under certain conditions, TGF-β1 exerted a co-stlmulatory effect on peripheral blood CD4+CD45RA+ T cells whereas the outgrowth of CD4+CD45RO+ T cells was suppressed in any activation system tested. The enhancement of prollferatlve responses by TGF-β1 in TCR/CD3 or CD2 stimulated cultures of CD45RA+ cells involved up-regulatlon of CD25 expression and was dependent on the presence of exogenous IL-2 or CD28 mAbs; IL-7 driven proliferatlve responses were suppressed by TGF-β1. These observations were confirmed in experiments with purified cord blood (CB) CD4+ T cells inasmuch as addition of TGF-β1 caused a 2- to 7-fold increase in IL-2 driven proliferatlve responses of these cells. Finally we show that, in contrast to the effect of TGF-β1 during primary stimulation of CB CD4+ T cells, TGF-β1 suppressed T cell proliferation for ∼40% in secondary cultures of these cell. Our findings indicate that TGF-β1 Is a blfunctlonal regulator of CD4+ T cell growth in vitro, with co-stimulatory capacities during CD45RA+ T cell mediated primary responses and growth suppresslve effects during secondary responses of CD45RO+ T cells.

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