Imbalance between T helper 1 and regulatory T cells plays a detrimental role in experimental Parkinson’s disease in mice

Abstract

Objective Parkinson’s disease (PD) is a degenerative disorder characterized by steady motor function loss. PD pathogenesis remains inconclusive, but aberrant immune responses might play important roles. We hypothesized that imbalance between T helper (Th) 1 and regulatory T (Treg) cells was essential in experimental PD. Methods Th1 and Treg cells from the blood of patients with PD and healthy volunteer blood were measured by flow cytometry. Experimental PD was induced in mice by peritoneal injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Experimental PD severity was measured by open field test behavior assessments (distance moved, rearing, and grooming). Mice were administered neutralizing anti-tumor necrosis factor (TNF) α to inhibit Th1 effects. Treg cells were depleted by anti-CD25 neutralizing antibodies or isolated and transferred to experimental PD mice. Results Patients with PD had fewer Treg and more Th1 cells than healthy volunteers. Experimental PD mice exhibited fewer Treg and more Th1 cells. Treg cell depletion exacerbated experimental PD, whereas TNFα neutralization attenuated PD in mice. Treg transfer to experimental PD mice reduced PD severity. Mechanistically, anti-TNFα antibody administration and Treg transfer increased Treg and reduced Th1 cell abundance in the brain. Conclusion Th1 and Treg cell imbalance plays an essential role in mouse experimental PD pathogenesis.