Table 1 Peripheral immune cell functions and mechanisms in AD
From: Peripheral and central neuroimmune mechanisms in Alzheimer’s disease pathogenesis
Immune cell type | Main function | Immune factors | References |
|---|---|---|---|
CD8+ T cells | Exacerbate neuroinflammation by secreting cytotoxic factors that activate microglia, leading to neuronal damage and neurodegeneration; increased CD8+ TEMRA cells correlate negatively with cognitive function | CCL2, CCL3, CCL4, CCL8, CXCL10, IFN-γ | |
CD4+ T cells - Th1 | Activate microglia to promote Aβ clearance; excessive activation exacerbates Aβ accumulation and neuroinflammation, leading to cognitive deficits | IFN-γ, TNF-α | |
CD4+ T cells - Th2 | Regulate immune response, reduce inflammation, promote microglial deactivation, alleviating Aβ burden and neuroinflammation | IFN-γ, TNF-α, GM-CSF, IL-2, IL-4 | |
CD4+ T cells - Th9 | IL-9, in combination with TGF-β1, promotes differentiation of naive CD4+ T cells into Th17 cells | IL-9 | |
CD4+ T cells - Th17 | Induce neuroinflammation; inhibit microglial Aβ clearance, accelerating memory impairment and Aβ accumulation | IL-17 A, IFN-γ, IL-23, IL-21, IL-6, TNF-α | |
CD4+ T cells - Th22 | Activates glial cells, promoting pro-inflammatory cytokine production and lymphocyte infiltration into brain parenchyma | IL-22 | [39] |
CD4+ T cells - Tregs | Modulate immune response through secretion of anti-inflammatory cytokines; enhancing Tregs function can be beneficial, while depletion may offer advantages in certain contexts; Tregs are reduced in AD patients | IL-10, TGF-β | |
B cells | Secrete anti-Aβ immunoglobulins, affecting Aβ accumulation; B cell depletion reduces disease progression, but early depletion accelerates cognitive decline, indicating a complex, stage-dependent role | ||
Macrophages | Involved in Aβ clearance; function declines with age; monocyte-derived macrophages infiltrate brain parenchyma in late-stage AD, potentially compromising BBB integrity | IL-1β, TNF-α | |
Natural killer cells | Function is complex; depletion provides neuroprotection while augmentation mitigates Aβ deposition and enhances cognitive performance | IL-2, IFN-γ | |
Neutrophils | Extravasate and accumulate in amyloid deposition regions, exacerbating AD pathology and contributing to cognitive decline; disrupt BBB integrity | IL-17, NETs | |
γδT cells | Accumulate in brain and meninges in AD models, associated with cognitive decline; contribute to neuroinflammation and early pathological progression | IL-17 A | |
MAIT cells | Elevated MR1 expression in AD brains; promote neuroinflammation and amyloid plaque formation; MR1 or MAIT cell deficiency slows amyloid plaque formation | MR1 |