The profile of cerebral T cells in dementia with Lewy bodies

Abstract

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative cause of dementia, behind Alzheimer’s disease (AD). Neuroinflammation has been implicated in the aetiology of AD, with the involvement of both innate and adaptive immune responses. A potential role for adaptive immune cells is supported by T cell recruitment into the brain parenchyma in AD, however, this has not yet been extensively investigated in DLB.
To determine the cerebral profile of T cells in DLB, a human post-mortem study was conducted to examine T cell populations in brain tissue from 30 DLB and 29 control cases using immunohistochemistry. Specific markers were used to identify T cell populations: CD4 (T helper cells), CD8 (T cytotoxic cells), Foxp3 (Treg), Tbet (T helper/cytotoxic 1 cells) and GATA3 (T helper/cytotoxic 2 cells). T cell numbers were quantified and categorised by location (grey or white matter) and compartment (parenchyma or perivascular). Markers of neuropathology and inflammation were correlated with T cell markers.
The study revealed increased numbers of CD4+ T cells in the grey matter parenchyma in DLB compared to controls. Although no significant difference was observed in the number of CD8+ T cells between groups, there was a trend towards increased numbers of CD8+ T cells in the DLB group. Within grey matter in DLB, the number of CD8+ T cells was associated with increased neuronal expression of CD32b. Further exploration of T cell subsets revealed increased numbers of Tbet+ and GATA3+ T cells in the grey matter parenchyma in DLB. In contrast, there was no significant difference in the number of Foxp3+ T cells between groups. Increased numbers of Tbet+ T cells were associated with increased expression of the inflammatory markers, CD64 and CD32b in DLB. No associations were found between CD4, Foxp3, GATA3 and markers of inflammation. Correlations with markers of neuropathology revealed no associations with any T cell marker.
This project provides evidence of an altered profile of T cells in the DLB brain with increased recruitment of CD4+ T cells into the grey matter parenchyma, potentially contributing to neuroinflammation and neurodegeneration in DLB. The increased presence of Tbet+ and GATA3+ T cells within the grey matter parenchyma implicate T helper 1 and T helper 2 cells as the infiltrating CD4+ T cell subsets. The association between Tbet+ T cells and CD64 may represent interactions with microglia to promote proinflammatory responses in DLB. Interactions between CD8+ and Tbet+ T cells with neurons are inferred by associations with CD32b, potentially contributing to synaptic dysfunction. The lack of association with markers of neuropathology in DLB suggests that T cell responses occur independently of neuropathological changes. Further exploration of T cell subsets in the brain, cerebrospinal fluid and blood compartments is warranted in DLB to improve our understanding of disease mechanisms and to guide the development of therapeutic strategies such as T cell modulation.

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Identifiers

ORCID for Claire Gee: orcid.org/0000-0002-2215-5949

ORCID for Jay Amin: orcid.org/0000-0003-3792-0428

ORCID for Delphine Boche: orcid.org/0000-0002-5884-130X

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