Changes in innate and acquired immune responses in mice with targeted deletion of the dopamine transporter gene.

The dopamine transporter (DAT) is responsible for the re-uptake of dopamine into presynaptic nerve terminals and thereby controls dopaminergic neurotransmission. Deletion of DAT results in a hyperdopaminergic phenotype and DAT(-/-) mice are characterized by pituitary hypoplasia, impaired maternal behavior, and increased locomotion. From earlier studies, we have evidence that the activity of the central dopaminergic system may play a role in determining immune reactivity and disease susceptibility. To further explore the functional relation between the dopaminergic system and the immune system, we investigated the activity of the immune system in DAT(-/-) mice. We show that in vitro, splenocytes from DAT(-/-) mice displayed reduced natural killer cell activity and reduced mitogen-induced cytokine responses. In contrast, LPS-induced cytokine production by macrophages was enhanced. In vivo, the cellular response to immunization with ovalbumine (OVA-induced delayed type hypersensitivity response) was significantly reduced. Interestingly, the OVA-induced humoral response (anti-OVA IgG) was increased in DAT(-/-) mice compared to wild-type animals. Plasma levels of catecholamines and corticosterone did not differ significantly between DAT(-/-) and wild-type animals. In conclusion, we show in the present study that interfering with the dopaminergic system has major consequences for both the acquired and the innate immune response.