CD6 attenuates early and late signaling events, setting thresholds for T-cell activation.
Bottom Line: Measuring calcium mobilization in single cells responding to superantigen, we found that human T cells expressing rat CD6 react significantly less well compared with T cells not expressing the exogenous receptor.Calcium responses, and also late indicators of T-cell activation such as IL-2 release, were also diminished in TCR-activated Jurkat cells expressing human CD6, compared with CD6-deficient cells or cells expressing a cytoplasmic deletion mutant of human CD6.Our data suggest that CD6 is a signaling attenuator whose expression alone, i.e. in the absence of ligand engagement, is sufficient to restrain signaling in T cells.
Affiliation: Group of Cell Activation and Gene Expression, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal.Show MeSH
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Mentions: To determine whether endogenous hCD6 would exhibit comparable inhibitory behavior in these cells, we suppressed its expression using hCD6-specific morpholino oligomers (MOs); we were successful in reducing expression by over 95% as assessed by western blotting (Fig. 2A). Using CD3 mAb (OKT3), we activated the untransfected T cells as well as T cells treated with the MOs, and measured calcium mobilization. At 1 μg/mL to activate 3×106 cells/mL, OKT3 induced a very modest increase in calcium in hCD6-expressing T cells, whereas a pronounced increase in calcium signaling was observed in the hCD6-depleted T cells (Fig. 2B), confirming the observations made for the rCD6 transfections.
Affiliation: Group of Cell Activation and Gene Expression, IBMC-Instituto de Biologia Molecular e Celular, Porto, Portugal.