Regulatory CD4+CD25+Foxp3+ T cells (Treg) have received significant attention for their role in controlling immune responses. Although knowledge of Treg biology has burgeoned, wide gaps remain in our understanding of Treg function under both normal and pathological conditions. Pioneering studies demonstrated roles for Treg in cancer and autoimmune diseases, including experimental autoimmune encephalitis, and this knowledge is often applied to other pathologies including neurodegenerative conditions. However, differences between immunity in neurodegeneration and in malignancy or autoimmunity are often neglected. Thus, Treg manipulations in CNS neurodegenerative conditions often yield unexpected outcomes. Here, we explore how the immunology of neurodegeneration differs from that of cancer and autoimmunity and how these differences create confusion about the role of Treg in neurodegenerative conditions.
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