TY - JOUR
T1 - Unaltered T cell responses to common antigens in individuals with Parkinson's disease
AU - Williams, Gregory P.
AU - Muskat, Kaylin
AU - Frazier, April
AU - Xu, Yaqian
AU - Mateus, José
AU - Grifoni, Alba
AU - da Silva Antunes, Ricardo
AU - Weiskopf, Daniela
AU - Amara, Amy W.
AU - Standaert, David G.
AU - Goldman, Jennifer G.
AU - Litvan, Irene
AU - Alcalay, Roy N.
AU - Sulzer, David
AU - Lindestam Arlehamn, Cecilia S.
AU - Sette, Alessandro
N1 - Funding Information:
The study is funded by the joint efforts of The Michael J. Fox Foundation for Parkinson's Research (MJFF) and the Aligning Science Across Parkinson's (ASAP) initiative, the NIH T32AI125179 (GPW), P50NS108675 (DGS, AWA), and the JPB Foundation (DS). MJFF administers the grant ASAP-000375 (CLA, DS) on behalf of ASAP and itself. For the purpose of open access, the author has applied a CC BY public copyright license to all Author Accepted Manuscripts arising from this submission.
Funding Information:
The study is funded by the joint efforts of The Michael J. Fox Foundation for Parkinson's Research (MJFF) and the Aligning Science Across Parkinson's (ASAP) initiative, the NIH T32AI125179 (GPW), P50NS108675 (DGS, AWA), and the JPB Foundation (DS). MJFF administers the grant ASAP-000375 (CLA, DS) on behalf of ASAP and itself. For the purpose of open access, the author has applied a CC BY public copyright license to all Author Accepted Manuscripts arising from this submission.
Publisher Copyright:
© 2022 The Authors
PY - 2023/1/15
Y1 - 2023/1/15
N2 - Background and objectives: Parkinson's disease (PD) is associated with a heightened inflammatory state, including activated T cells. However, it is unclear whether these PD T cell responses are antigen specific or more indicative of generalized hyperresponsiveness. Our objective was to measure and compare antigen-specific T cell responses directed towards antigens derived from commonly encountered human pathogens/vaccines in patients with PD and age-matched healthy controls (HC). Methods: Peripheral blood mononuclear cells (PBMCs) from 20 PD patients and 19 age-matched HCs were screened. Antigen specific T cell responses were measured by flow cytometry using a combination of the activation induced marker (AIM) assay and intracellular cytokine staining. Results: Here we show that both PD patients and HCs show similar T cell activation levels to several antigens derived from commonly encountered human pathogens/vaccines in the general population. Similarly, we also observed no difference between HC and PD in the levels of CD4 and CD8 T cell derived cytokines produced in response to any of the common antigens tested. These antigens encompassed both viral (coronavirus, rhinovirus, respiratory syncytial virus, influenza, cytomegalovirus) and bacterial (pertussis, tetanus) targets. Conclusions: These results suggest the T cell dysfunction observed in PD may not extend itself to abnormal responses to commonly encountered or vaccine-target antigens. Our study supports the notion that the targets of inflammatory T cell responses in PD may be more directed towards autoantigens like α-synuclein (α-syn) rather than common foreign antigens.
AB - Background and objectives: Parkinson's disease (PD) is associated with a heightened inflammatory state, including activated T cells. However, it is unclear whether these PD T cell responses are antigen specific or more indicative of generalized hyperresponsiveness. Our objective was to measure and compare antigen-specific T cell responses directed towards antigens derived from commonly encountered human pathogens/vaccines in patients with PD and age-matched healthy controls (HC). Methods: Peripheral blood mononuclear cells (PBMCs) from 20 PD patients and 19 age-matched HCs were screened. Antigen specific T cell responses were measured by flow cytometry using a combination of the activation induced marker (AIM) assay and intracellular cytokine staining. Results: Here we show that both PD patients and HCs show similar T cell activation levels to several antigens derived from commonly encountered human pathogens/vaccines in the general population. Similarly, we also observed no difference between HC and PD in the levels of CD4 and CD8 T cell derived cytokines produced in response to any of the common antigens tested. These antigens encompassed both viral (coronavirus, rhinovirus, respiratory syncytial virus, influenza, cytomegalovirus) and bacterial (pertussis, tetanus) targets. Conclusions: These results suggest the T cell dysfunction observed in PD may not extend itself to abnormal responses to commonly encountered or vaccine-target antigens. Our study supports the notion that the targets of inflammatory T cell responses in PD may be more directed towards autoantigens like α-synuclein (α-syn) rather than common foreign antigens.
KW - Bacterial immunity
KW - Immune system
KW - Inflammation
KW - Neurodegeneration
KW - Neuroimmunology
KW - Parkinson's disease
KW - T cells
KW - Viral immunity
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UR - http://www.scopus.com/inward/citedby.url?scp=85143877907&partnerID=8YFLogxK
U2 - 10.1016/j.jns.2022.120510
DO - 10.1016/j.jns.2022.120510
M3 - Article
C2 - 36495691
AN - SCOPUS:85143877907
SN - 0022-510X
VL - 444
JO - Journal of the Neurological Sciences
JF - Journal of the Neurological Sciences
M1 - 120510
ER -