T Cell Mediated Neuroprotection by Therapeutic Vaccination for Parkinson's Disease

Parkinson's disease is a progressive neurodegenerative disorder whereby the neurons of the brain that control movement die. Although the events that initiate the death of those neurons remain unknown, the resulting inflammation perpetuates a hostile environment for the remaining neurons and facilitates their eventual demise. In disease models, inhibition of inflammation by drugs and genetic modifications has been shown to be neuroprotective.

Our long-term objective is to interdict the inflammatory response by modulating the immune system to alleviate the hostile environment associated with this inflammatory response. We previously demonstrated that immune cells from donors immunized with glatiramer acetate, a peptide polymer similar to neuronal proteins and currently approved for use in multiple sclerosis, inhibit inflammation and neuronal death in our model of Parkinson's disease. Further analysis indicated that the immune cells responsible for this neuroprotective response were T lymphocytes, a subset of white blood cells that are involved in orchestrating immune responses. However, which of the many functionally different T lymphocyte subsets are involved, remains to be determined.

These studies propose to isolate and expand different T lymphocyte subsets which secrete specific anti-inflammatory or inflammatory factors, and assess these subsets for their capacity to suppress inflammation and inhibit neuronal death in models of inflammation and neuronal degeneration simulating those found in Parkinson's disease. These data will provide information to understand the immune responses required to inhibit neuroinflammation and neuronal death such that vaccine or immune-modulating strategies may be devised for incorporation into clinical trials for Parkinson disease.