Lipopolysaccharide-dependent down-regulation of CD27 expression on T cellsactivated with superantigen

To investigate the mechanisms underlying T-cell responses during superantig en (SAg) stimulation, we analysed the effects of SAg on CD27 expression wit h or without lipopolysaccharide (LPS) as a novel regulator of T-cell functi on. CD27 is expressed on the majority of resting peripheral blood T cells ( CD27(low)). Activation of T cells by SAg induces high levels of CD27 surfac e expression (CD27(high)) accompanied with simultaneous CD30 receptor expre ssion. After prolonged activation in vitro, the level of CD27 expression be came intermediate. The effects of LPS on down-regulation of CD27(high) expr ession on CD30(+) T cells were dose-dependent. Separating LPS-stimulated mo nocytes from T cells by mechanical dispersion abolished its inhibitory effe ct, indicating the requirement for direct interactions between monocytes an d T cells. We also found that SAg up-regulated CD80 expression on CD14(+) m onocytes and LPS inhibited SAg-induced CD80 expression after 24 hr of stimu lation. Up-regulation of CD152 (CTLA-4) was selective, since it was found t o be preferentially expressed on the CD30(+) population. Competitive experi ments using soluble blocking peptides showed that addition of CD28 or CD80 peptide recovered LPS-induced down-regulation of CD27(high) expression on C D30(+) T cells. These observations suggested that the presence of low level s of CD80 on monocytes may partially inhibit CD27 expression due to ineffic ient delivery of positive signals via CD28/CD80 interaction, and that the i ncreased levels of CD80 enhance the inhibition through interactions with CD 152 which is expressed at the highest levels after 48 hr of activation.