The DOI matches its Crossref record; 76 of the 76 references it cites were found in a registry or an index.
CD4 T Cells Induce A Subset of MHCII-Expressing Microglia that Attenuates Alzheimer Pathology
Open accessAbstract
Microglia play a key role in innate immunity in Alzheimer disease (AD), but their role as antigen-presenting cells is as yet unclear. Here we found that amyloid β peptide (Aβ)-specific T helper 1 (Aβ-Th1 cells) T cells polarized to secrete interferon-γ and intracerebroventricularly (ICV) injected to the 5XFAD mouse model of AD induced the differentiation of major histocompatibility complex class II (MHCII)+ microglia with distinct morphology and enhanced plaque clearance capacity than MHCII- microglia. Notably, 5XFAD mice lacking MHCII exhibited an enhanced amyloid pathology in the brain along with exacerbated innate inflammation and reduced phagocytic capacity. Using a bone marrow chimera mouse model, we showed that infiltrating macrophages did not differentiate to MHCII+ cells following ICV injection of Aβ-Th1 cells and did not support T cell-mediated amyloid clearance. Overall, we demonstrate that CD4 T cells induce a P2ry12+ MHCII+ subset of microglia, which play a key role in T cell-mediated effector functions that abrogate AD-like pathology.
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“MHCII+ microglia exhibited higher rates of phagocytosis than their MHCII− counterparts in 5xFAD mice (60).”
From Reducing microglial lipid load enhances β amyloid phagocytosis in an Alzheimer’s disease mouse model (2025) · cites this paper as [60]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
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“It has previously been shown that the depletion of T cells, B cells, and natural killer (NK) cells contributes to an increase in Aβ deposition [4–6].”
From Control of the temporal development of Alzheimer’s disease pathology by the MR1/MAIT cell axis (2023) · cites this paper as [6]
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“a recent study found that 5XFAD mice that lack MHC class II expression exhibit increased amyloid pathology, 21”
From The P522R protective variant of PLCG2 promotes the expression of antigen presentation genes by human microglia in an Alzheimer's disease mouse model (2022) · cites this paper as [21]
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“Notably, the loss of MHC class II molecules has been shown to increase Aβ plaques [3, 6].”
From Control of the temporal development of Alzheimer’s disease pathology by the MR1/MAIT cell axis (2023) · cites this paper as [6]
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“Adoptive transfer of T helper 1 (Th1) cells into AD model mice results in a decrease in the amount of Aβ [6].”
From Control of the temporal development of Alzheimer’s disease pathology by the MR1/MAIT cell axis (2023) · cites this paper as [6]
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Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke
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Tangle and neuron numbers, but not amyloid load, predict cognitive status in Alzheimer’s disease
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Metadata
- Authors
- Mittal, K., Eremenko, E., Berner, O., Elyahu, Y., Strominger, I., Apelblat, D., Nemirovsky, A., Spiegel, I., & Monsonego, A.
- Affiliations
- Ben-Gurion University of the Negev (IL)
- Weizmann Institute of Science (IL)
- Corresponding author
- Monsonego, Alon
- ORCID
- Venue
- iScience
- Publisher
- Elsevier BV
- Published
- 2019-06
- Volume
- 16
- Pages
- 298-311
- ISSN
- 2589-0042 (ISSN-L)
- PMC
- PMC6581663
- OpenAlex
- W2947933080
- Cited by
- 114
- References
- 76
- Citations by year
- 2026: 13 · 2025: 17 · 2024: 28 · 2023: 17 · 2022: 16 · 2021: 10 · 2020: 13
- FWCI
- 4.29
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- iScience (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Israel Science Foundation (684/14)
- Litwin and Gural Foundations
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Alzheimer's disease research and treatments
- Health Sciences › Medicine › Clinical Neurology › Multiple Sclerosis Research Studies
- Keywords
- Alzheimer's disease, microglia, CD4+ T cells, MHC class II, amyloid-beta, Th1 cells, interferon-gamma, amyloid plaque clearance, P2Y12 receptor, 5xFAD mice, innate immunity, phagocytosis, bone marrow chimeras, infiltrating macrophages
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