Lymphocytes reduce nigrostriatal deficits in the 6-hydroxydopamine mouse model of Parkinson's disease.

Neuroinflammation is a well-known neuropathological feature of Parkinson's disease (PD), but it remains controversial whether it is causal or consequential to neurodegeneration. While the role of microglia in the pathogenesis has been thoroughly investigated in human and different rodent models, data concerning the impact of the adaptive immune system on the pathogenesis of PD are still rare, although lymphocyte populations were found in brain tissue of PD patients and have been implicated in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mediated neurodegeneration in mice. To test the hypothesis that the adaptive immune system contributes to the progression of PD in the murine 6-hydroxydopamine (6-OHDA) model, we performed unilateral 6-OHDA injection into the medial forebrain bundle and compared wild-type mice with recombination activating gene-1 deficient mice (RAG-1(-/-)), that lack mature lymphocytes. After 6-OHDA injection, immune-deficient mice moved significantly slower and less often than wild-type mice. Rotarod analysis displayed a shorter latency to fall in RAG-1(-/-) mice. Immunohistochemical analysis in wild-type mice demonstrated a higher CD8+ T cell density in the ipsilesional striatum compared to sham-operated animals. Cell counts of tyrosine hydroxylase positive dopaminergic neurons of the substantia nigra in immune compromised mice were significantly reduced compared to wild-type mice. Wild type bone marrow reconstitution into RAG-1(-/-) recipients rescued the clinical deterioration as well as the neurodegeneration in RAG-1(-/-) deficient recipients ameliorated clinical symptoms and neurodegeneration after 6-OHDA treatment. Our data indicate that lymphocytes reduce the clinical and neuropathological impact of 6-OHDA lesioning and thus may play a protective role in this toxic mouse model of PD.