@article{e9d6b2d6659b4b6eaba2feaac948a379,
title = "CD4+ regulatory and effector/memory T cell subsets profile motor dysfunction in Parkinson's disease",
abstract = "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.",
keywords = "CD4, Immune activation, Motor function, Parkinson's disease, T cells, Teff, Treg",
author = "Saunders, {Jessica A.Hutter} and Estes, {Katherine A.} and Kosloski, {Lisa M.} and Allen, {Heather E.} and Dempsey, {Kathryn M.} and Torres-Russotto, {Diego R.} and Meza, {Jane L.} and Santamaria, {Pamela M.} and Bertoni, {John M.} and Murman, {Daniel L.} and Ali, {Hesham H.} and Standaert, {David G.} and Mosley, {R. Lee} and Gendelman, {Howard E.}",
note = "Funding Information: Acknowledgments We would like to thank the University of Nebraska Medical Center Cell Analysis Facility staff for flow cytometric data acquisition and excellent technical advice; Max Kuenstling, David Stone, Kristi Anderson, Duy Ha, and Jim Terry for technical assistance or discussion; the nursing staff at Neurological Consultants of Nebraska, the Department of Neurological Sciences at the University of Nebraska Medical Center, and the Department of Neurology at the University of Alabama at Birmingham for enrolling and monitoring patients and drawing blood for testing. We would also like to thank all of the participating PD patients and their caregivers for making this study possible. This work was supported by an Innovation grant from the Michael J. Fox Foundation for Parkinson{\textquoteright}s Research (H.E.G. and D.G.S.). Other support for this project was provided through the Francine and Louis Blumkin Foundation, the Community Neuroscience Pride of Nebraska Research Initiative, the Carol Swarts, M.D., Laboratory of Emerging Neuroscience Research, the Alan Baer Charitable Trust (H.E.G.), Schumacher Foundation (D.T.) and National Institutes of Health grants R01 NS070190 (R.L.M), P20 DA026146, 5P01 DA028555-02, R01 NS36126, P01 NS31492, 2R01 NS034239, P20 RR15635, P01 MH64570, P01 NS43985 (H.E.G.), and F31 NS076017 (H.E.A.); and a Community Fast Track grant from the Michael J. Fox Foundation for Parkinson{\textquoteright}s Research (R.L.M.).",
year = "2012",
month = dec,
doi = "10.1007/s11481-012-9402-z",
language = "English (US)",
volume = "7",
pages = "927--938",
journal = "Journal of Neuroimmune Pharmacology",
issn = "1557-1890",
publisher = "Springer New York",
number = "4",
}