Pramipexole promotes CD8+ regulatory T cell-dependent neuroprotection in Parkinson's disease patients.
Pramipexole promotes CD8+ regulatory T cell-dependent neuroprotection in Parkinson's disease patients.
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Original abstract
BACKGROUND: Parkinson's disease (PD) is caused by the death of dopaminergic neurons. Since immune system cells express dopamine receptors, dopaminergic agonists may modify their function. However, the effects of dopaminergic agonists on immunoregulation and the specific dopamine receptors involved are unknown. OBJECTIVE: This study will examine the effects of pramipexole treatment on dopamine receptor expression and immunosuppressive activity of CD8+ Tregs, as well as its neuroprotective effects. MATERIAL AND METHODS: Dopamine receptor expression was determined in patients treated with pramipexole and in control subjects. PBMCs from controls were stimulated with anti-CD3/CD28 alone or with 2-200 ng/mL of pramipexole for 24 h. CD8+ T cell immunosuppressive capacity in both groups was evaluated using flow cytometry. CD8+ Tregs were pretreated with pramipexole and co-cultured with dopaminergic neurons previously exposed to 6-OHDA. Neuroprotective capacity was defined by the survival of Tyrosine Hydroxylase-positive neurons, as determined by immunofluorescence. RESULTS: Pramipexole treatment increased the proportion of CD8+ T cells expressing D2 receptors, and in vitro studies showed similar results. The suppressive function of CD8+ Tregs was similar in patients treated with pramipexole and control subjects. This suggests that dopaminergic treatment compensates for the reduction in the number of CD8+ Tregs. Pramipexole (20 and 200 ng/mL) increased the suppressive function of CD8+ Tregs. CD8+ Tregs stimulated with 2 or 20 ng/mL of pramipexole exhibited a neuroprotective effect on dopaminergic neurons challenged with 6-OHDA. CONCLUSION: Pramipexole increased the percentage of CD8+ T cells expressing the D2 receptor on their cell membranes. Treatment of CD8+ Tregs improved their immunosuppressive function and had a neuroprotective effect. Therefore, in addition to its previously reported direct effects on neurons and glial cells, treatment with pramipexole may also exert immunomodulatory effects on CD8+ regulatory T cells.