CD4+ T Cell Subsets in CNS Disorders: Pathogenic Roles, Immune Dysregulation, and Therapeutic Perspectives.

Abstract

The central nervous system (CNS), previously considered immune-isolated due to the blood-brain barrier (BBB) and absence of lymphatic drainage, is now understood as a dynamic interface with the peripheral immune system. CNS neurons and glia actively modulate immune responses, and circulating T cells survey and sometimes infiltrate this privileged site. While essential for host defense and tissue homeostasis, dysregulated immune surveillance may contribute to chronic neuroinflammation and, in specific disease contexts, autoimmune pathology. A key question is how T cell responses are initiated in the CNS, given its limited antigen presentation. This review synthesizes current evidence on the pathogenic and protective roles of Th1, Th2, Th17, and Treg cells across autoimmune demyelinating and neurodegenerative CNS disorders, with a focus on multiple sclerosis (MS), Alzheimer's disease (AD), and Parkinson's disease (PD). We also evaluate emerging T cell-targeted immunotherapies and their potential to rebalance CNS immunity and impede disease progression.