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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2022

Open Access 01-12-2022 | Parkinson's Disease | Research

Expansion of regulatory T cells by CD28 superagonistic antibodies attenuates neurodegeneration in A53T-α-synuclein Parkinson’s disease mice

Authors: Mohammad Badr, Rhonda L. McFleder, Jingjing Wu, Susanne Knorr, James B. Koprich, Thomas Hünig, Jonathan M. Brotchie, Jens Volkmann, Manfred B. Lutz, Chi Wang Ip

Published in: Journal of Neuroinflammation | Issue 1/2022

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Abstract

Background

Regulatory CD4+CD25+FoxP3+ T cells (Treg) are a subgroup of T lymphocytes involved in maintaining immune balance. Disturbance of Treg number and impaired suppressive function of Treg correlate with Parkinson’s disease severity. Superagonistic anti-CD28 monoclonal antibodies (CD28SA) activate Treg and cause their expansion to create an anti-inflammatory environment.

Methods

Using the AAV1/2-A53T-α-synuclein Parkinson’s disease mouse model that overexpresses the pathogenic human A53T-α-synuclein (hαSyn) variant in dopaminergic neurons of the substantia nigra, we assessed the neuroprotective and disease-modifying efficacy of a single intraperitoneal dose of CD28SA given at an early disease stage.

Results

CD28SA led to Treg expansion 3 days after delivery in hαSyn Parkinson’s disease mice. At this timepoint, an early pro-inflammation was observed in vehicle-treated hαSyn Parkinson’s disease mice with elevated percentages of CD8+CD69+ T cells in brain and increased levels of interleukin-2 (IL-2) in the cervical lymph nodes and spleen. These immune responses were suppressed in CD28SA-treated hαSyn Parkinson’s disease mice. Early treatment with CD28SA attenuated dopaminergic neurodegeneration in the SN of hαSyn Parkinson’s disease mice accompanied with reduced brain numbers of activated CD4+, CD8+ T cells and CD11b+ microglia observed at the late disease-stage 10 weeks after AAV injection. In contrast, a later treatment 4 weeks after AAV delivery failed to reduce dopaminergic neurodegeneration.

Conclusions

Our data indicate that immune modulation by Treg expansion at a timepoint of overt inflammation is effective for treatment of hαSyn Parkinson’s disease mice and suggest that the concept of early immune therapy could pose a disease-modifying option for Parkinson’s disease patients.
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Metadata
Title
Expansion of regulatory T cells by CD28 superagonistic antibodies attenuates neurodegeneration in A53T-α-synuclein Parkinson’s disease mice
Authors
Mohammad Badr
Rhonda L. McFleder
Jingjing Wu
Susanne Knorr
James B. Koprich
Thomas Hünig
Jonathan M. Brotchie
Jens Volkmann
Manfred B. Lutz
Chi Wang Ip
Publication date
01-12-2022
Publisher
BioMed Central
Published in
Journal of Neuroinflammation / Issue 1/2022
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-022-02685-7

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