Immune Cell Traffic in the Brain: Blundering and Migration of Autoreactive T Lymphocytes

Abstract

The migration of an autoreactive CD4 T lymphocyte across the blood-brain barrier (BBB) represents a crucial step in the pathogenesis of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalitis (EAE). For a naive, autoreactive T lym phocyte to enter the CNS, it must first be activated by antigen presented by an anti gen-presenting cell in peripheral lymphoid tissue. Effector lymphocytes home to activated endothelium in the CNS and other tissues through the binding of the integrins very late antigen 4 (VLA-4) and leukocyte function antigen 1 (LFA-1) to vascular cell adhesion molecule (VCAM-1) and intercellular cell adhesion molecule (lCAM-1), respectmely. Al though VLA-4 and LFA-1 clearly mediate T cell recruitment in a region of established inflammation, the mechanisms of early lymphocyte entry prior to endothelial activation remain unclear. Here, it is hypothesized that initiation of an inflammatory focus in CNS autoimmune disease is mediated by a novel cell adhesion pathway that is VLA-4-inde pendent and permits autoreactive lymphocytes to randomly "blunder" into the brain. An understanding of these mechanisms is crucial to the development of antigen-nonspecific therapies for MS. NEUROSCIENTIST 3:207-210, 1997

Keywords

Homing CD4 T lymphocyte Multiple sclerosis EAE

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