Cutting edge:: Stimulation of dopamine D4 receptors induce T cell quiescence by up-regulating Kruppel-like factor-2 expression through inhibition of ERK1/ERK2 phosphorylation

The neurotransmitter dopamine (DA) is an important regulator of human T cell functions. Although it has been observed that DA, by acting through the D-1/D-5, D-2, and D-3 receptors, can activate resting T cells by stimulating the release of cytokines and the expression of surface integrins and also inhibit the proliferation of activated T cells by down-regulating nonreceptor tyrosine kinases, there is not yet a report indicating the functional significance of the D-4 DA receptors present in these cells. The present work,for the first time, demonstrates that the stimulation of D-4 DA receptors in human T cells induces T cell quiescence by up-regulating lung Kruppel-like factor-2 expression through the inhibition of ERK1/ERK2 phosphorylation. These results reveal a new link between the nervous system and T cell quiescence and indicate that D-4 DA receptor agonists may have a therapeutic value in diseases with uncontrolled T cell proliferation. The Journal of Immunology, 2006, 177: 7525-7529.