CD28 Costimulation Induces δ Opioid Receptor Expression During Anti-CD3 Activation of T Cells

Previous studies have demonstrated that naive splenic mouse T cells express no or only very low levels of the δ-type opioid receptor (δOR), but stimulation of mouse splenocytes with Con A results in induction of δOR mRNA and protein. In this report we have shown that stimulation of highly purified populations of naive mouse T cells with anti-CD3 mAb alone results in T cell activation, as evidenced by sustained IL-2 secretion and cell proliferation, but fails to elicit δOR expression. However, δOR expression is induced by costimulation of these very pure T cells with anti-CD3 and anti-CD28 mAbs. The δOR induction by anti-CD3 and anti-CD28 costimulation was completely blocked by inhibition of phosphatidylinositol 3-kinase with wortmannin. Because phosphatidylinositol 3-kinase activation in T cells is linked to costimulation, these results suggest that induction of δOR expression during T cell activation is strictly dependent on costimulation. It also appears that costimulatory receptors other than CD28 can provide the signaling required for δOR expression because δOR mRNA was induced by Con A stimulation of splenocytes from CD28-deficient mice.