Differential effect of transforming growth factor-beta 1 on the activation of human naive and memory CD4+ T...

Transforming growth factor-beta 1 (TGF-beta 1) can have stimulatory or inhibitory effects on cell growth. For several cell types, the effect of TGF-beta 1 was found to correlate with the differentiation stage of the cells and the presence of other cytokines. We have studied here the influence of TGF-beta 1 on CD4+ T cell activation in relation to the differentiation stage of the cells by evaluating the effect of TGF-beta 1 on the proliferative responses of purified CD4+CD45RA+ (unprimed) and CD4+CD45RO+ (primed) lymphocytes. Under certain conditions, TGF-beta 1 exerted a co-stimulatory 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 proliferative responses by TGF-beta 1 in TCR/CD3 or CD2 stimulated cultures of CD45RA+ cells involved up-regulation of CD25 expression and was dependent on the presence of exogenous IL-2 or CD28 mAbs; IL-7 driven proliferative responses were suppressed by TGF-beta 1. These observations were confirmed in experiments with purified cord blood (CB) CD4+ T cells inasmuch as addition of TGF-beta 1 caused a 2- to 7-fold increase in IL-2 driven proliferative responses of these cells. Finally we show that, in contrast to the effect of TGF-beta 1 during primary stimulation of CD CD4+ T cells, TGF-beta 1 suppressed T cell proliferation for approximately 40% in secondary cultures of these cells.(ABSTRACT TRUNCATED AT 250 WORDS)