Dual effect of CD4⁺CD25⁺regulatory T cells in neurodegeneration: A dialogue with microglia

Abstract

autoimmunity ͉ neuroprotection ͉ neurodegenerative conditions ͉ hippocampal slice cultures ͉ immune regulation T he systemic adaptive T cell-dependent immune response plays a key role in the ability of neurons in the central nervous system (CNS) to withstand injurious conditions (1-3). Studies from our laboratory have shown that, after a CNS injury, T cells nonselectively migrate to the site of injury (4), and suggest that homing T cells, which encounter their relevant antigens at the lesion site, are the ones that contribute to the repair. Such T cells become locally activated to produce neurotrophic factors (5) and cytokines, which are capable of affecting the activity of resident microglia and hence the fate of threatened neurons. We further showed that the T cell-dependent protection evoked after an axonal injury, being an anti-self-response (6), is constitutively limited by naturally occurring CD4 ϩ CD25 ϩ regulatory T cells (Treg) (6). It is, however, amenable to therapeutic boosting, either by postinjury immunization with antigens derived from dominant proteins residing in the site of damage or by depletion of Treg (2).Treg comprise Ϸ10% of the CD4 ϩ T cell population, and have been widely viewed as safeguards against the pathogenic effects of autoimmune CD4 ϩ CD25

Copolymer-1 Induces Adaptive Immune Anti-inflammatory Glial and Neuroprotective Responses in a Murine Model of HIV-1 Encephalitis

“…Foxp3 expression in COP-1-immunized animals suggests the presence of a regulatory T cell pool (83) in the lymphocyte population around the injected area. The increase in regulatory T cells in COP-1-treated animals demonstrates the importance of specific T cell subsets in neuroprotective and anti-inflammatory activities in neurologic and neuropsychiatric disorders (84,85). BDNF expression was significantly increased in HIVE animals after COP-1 treatment around the lesion areas.…”

Invasion of Hematopoietic Cells into the Brain of Amyloid Precursor Protein Transgenic Mice

“…Recent studies suggest indeed a regulatory interaction between T-cells and microglia, in which T-cells limit the destructive potential of the inflammatory reaction (Carson et al, 1999;Kipnis et al, 2004). Thus, the role of T-cells in the AD brain remains speculative; T-cells are present but do not show any association with tissue damage.…”

Regulatory T Cells Interfere with Glutathione Metabolism in Dendritic Cells and T Cells

“…Tregs (CD4 ϩ CD25 ϩ ) and Tn cells (CD4 ϩ CD25 Ϫ ) were isolated from mouse spleen and lymph nodes by magneticactivated cell sorting using an AutoMACS sorter (Miltenyi Biotec) as described (9,21). For activation of Teffs, purified Tn cells were cultured in 24-well plates (1 ml) supplemented with 1 M ovalbumin-(323-329) (OVA 323-329 ) antigen and irradiated splenocyte feeders (1:3) or DCs (2:1).…”