Opioid receptor expression and intracellular signaling by cells involved in host defense and immunity

More than two decades ago, Joseph Wybran reported his original insights on the expression of different opioid receptor types by T-cells. This was based on the differential effects that morphine and methionine enkephalin exerted on human T-cell rosetting in the presence of sheep red blood cells. Since that time, numerous laboratories have shown that opiate alkyloids and opioid peptides have pleiotropic effects on immune function. In general, these compounds act as immunomodulators that modify the immune response to mitogens, antigens and antibodies that cross-link the T-cell receptor. In the past decade, it has become clear that cells involved in host defense and immunity express the various mRNAs encoding the same opioid receptors originally identified in neuronal tissues. Recently, indirect fluorescence and immunofluorescence have been utilized to demonstrate the regulated expression of both delta and kappa opioid receptors, predominantly on T-cells. In addition, immune cells express sites that show atypical opiate and opioid binding properties. In this review, we will distill the evidence for both classical and atypical opioid receptors and their effects on signaling within immune cells, focusing on the T-cell and emphasizing the delta opioid receptor.