CD4+ regulatory and effector/memory T cell subsets profile motor dysfunction in Parkinson's disease.
Animal models and clinical studies have linked the innate and adaptive immune system to the pathology of Parkinson's disease (PD). Despite such progress, the specific immune responses that influence disease progression have eluded investigators. Herein, we assessed relationships between T cell phenotype and function with PD progression. Peripheral blood lymphocytes from two separate cohorts, a discovery cohort and a validation cohort, totaling 113 PD patients and 96 age- and environment-matched caregivers were examined by flow cytometric analysis and T cell proliferation assays. Increased effector/memory T cells (Tem), defined as CD45RO+ and FAS+ CD4+ T cells and decreased CD31+ and α4β7+ CD4+ T cells were associated with progressive Unified Parkinson's Disease Rating Scale III scores. However, no associations were seen between immune biomarkers and increased age or disease duration. Impaired abilities of regulatory T cells (Treg) from PD patients to suppress effector T cell function was observed. These data support the concept that chronic immune stimulation, notably Tem activation and Treg dysfunction is linked to PD pathobiology and disease severity, but not disease duration. The association of T cell phenotypes with motor symptoms provides fresh avenues for novel biomarkers and therapeutic designs.
Department of Pharmacology and Experimental Neuroscience, Center for Neurodegenerative Disorders, University of Nebraska Medical Center, Omaha, NE 68198-5880, USA.
Jessica A Hutter
JA
Saunders
Katherine A
KA
Estes
Lisa M
LM
Kosloski
Heather E
HE
Allen
Kathryn M
KM
Dempsey
Diego R
DR
Torres-Russotto
Jane L
JL
Meza
Pamela M
PM
Santamaria
John M
JM
Bertoni
Daniel L
DL
Murman
Hesham H
HH
Ali
David G
DG
Standaert
R Lee
RL
Mosley
Howard E
HE
Gendelman
D001772:Blood Cell Count; D015496:CD4-Positive T-Lymphocytes / Q000378:metabolism / Q000473:pathology*; D015331:Cohort Studies; D019295:Computational Biology; D005434:Flow Cytometry; D015870:Gene Expression / Q000502:physiology; D006801:Humans; D015850:Interleukin-6 / Q000096:biosynthesis; D016906:Interleukin-9 / Q000096:biosynthesis; D009000:Monocytes / Q000473:pathology; D009069:Movement Disorders / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D010641:Phenotype; D016176:T-Lymphocyte Subsets / Q000378:metabolism / Q000473:pathology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
D015850:Interleukin-6; D016906:Interleukin-9; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7