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Swift Entry of Myelin-Specific T Lymphocytes into the Central Nervous System in Spontaneous Autoimmune Encephalomyelitis

2008; American Association of Immunologists; Volume: 181; Issue: 7 Linguagem: Inglês

10.4049/jimmunol.181.7.4648

1550-6606

Gláucia C. Furtado, Maria Cecília Garibaldi Marcondes, Jo‐Ann Latkowski, Julia Tsai, Allen Wensky, Juan J. Lafaille,

Cell Adhesion Molecules Research

Abstract Strong evidence supports that CNS-specific CD4+ T cells are central to the pathogenesis of multiple sclerosis and experimental autoimmune encephalomyelitis (EAE). Using a model of spontaneous EAE, we demonstrated that myelin basic protein (MBP)-specific CD4+ T cells up-regulate activation markers in the CNS-draining cervical lymph nodes at a time when there is no T cell activation anywhere else, including the CNS, and before the appearance of clinical signs. In spontaneous EAE, the number of MBP-specific T cell numbers does not build up gradually in the CNS; instead, a swift migration of IFN-γ-producing T cells into the CNS takes place ∼24 h before the onset of neurological signs of EAE. Surgical excision of the cervical lymph nodes in healthy pre-EAE transgenic mice delayed the onset of EAE and resulted in a less severe disease. In EAE induced by immunization with MBP/CFA, a similar activation of T cells in the draining lymph nodes of the injection site precedes the disease. Taken together, our results suggest that peripheral activation of T cells in draining lymph nodes is an early event in the development of EAE, which paves the way for the initial burst of IFN-γ-producing CD4+ T cell into the CNS.