PD1 Negative and PD1 Positive CD4+ T Regulatory Cells in Mild Cognitive Impairment and Alzheimer's Disease

Regulatory T lymphocytes (T_reg) play a fundamental importance in modulating the relative balance between inflammation and immune tolerance, and alterations of these cells are observed in inflammatory diseases. To better characterize the neuroinflammatory processes suggested to be associated with Alzheimer's disease (AD) and to clarify the possible role of T_reg cells in this process, we extensively analyzed these cells (CD4 + CD25^highFoxp3+) in patients with either severe AD (n = 25) or mild cognitive impairment (MCI) (n = 25), comparing the results with those of two groups of healthy controls (HC) (n = 55). Because the intra- or extracellular expression of programmed death receptor 1 (PD1) identifies functionally diverse subsets of T_reg we also analyzed such subpopulations. Results showed that, whereas both T_reg and PD1^pos T_reg are increased in MCI and AD patients compared to HC, PD1^neg T_reg, the subpopulation of T_reg cells endowed with the strongest suppressive ability, are significantly augmented in MCI patients alone. In these patients amyloid-β-stimulated-T cells proliferation was reduced and T_reg-mediated suppression was more efficient compared to both AD and HC. The observation that PD1^neg T_reg, cells are increased in MCI patients reinforces the inflammatory origin of AD and supports a possible beneficial role of these cells in MCI that is lost in patients with full-blown AD.