CD4+ T cells from Copolymer-1 immunized mice protect dopaminergic neurons in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine model of Parkinson's disease.
Adoptive transfer of lymphoid cells from Copolymer 1 (Cop-1) immunized mice leads to T cell accumulation within the substantia nigra, modulation of microglial responses, upregulation of glial cell derived neurotrophic factor, and protection of the nigrostriatum following 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxication. We now demonstrate that T cells isolated from lymph nodes and spleens of Cop-1 immunized animals protect the nigrostriatal system from MPTP-induced neurodegeneration in a dose-dependent manner. CD4+ T cells elicited the most significant neuroprotective response while high titers of anti-Cop-1 antibodies showed no effect. These data further support the use of immunomodulatory strategies for Parkinson's disease.
Laurie
Chad
C
Center for Neurovirology and Neurodegenerative Disorders, Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, USA.
Reynolds
Ashley
A
Coskun
Ozlem
O
Bowman
Erik
E
Gendelman
Howard E
HE
Mosley
R Lee
RL
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D019264:Adoptive Transfer / Q000379:methods; D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology*; D002945:Cisplatin; D003342:Corpus Striatum / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005434:Flow Cytometry / Q000379:methods; D000068717:Glatiramer Acetate; D007069:Ifosfamide; D008297:Male; D051379:Mice; D016685:Mitomycin; D009474:Neurons / Q000502:physiology*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology / Q000628:therapy; D010455:Peptides / Q000276:immunology / Q000627:therapeutic use*; D013378:Substantia Nigra / Q000473:pathology; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D010455:Peptides; D016685:Mitomycin; D000068717:Glatiramer Acetate; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D014446:Tyrosine 3-Monooxygenase; D002945:Cisplatin; D007069:Ifosfamide; D004298:Dopamine