Swift entry of myelin-specific T lymphocytes into the central nervous system in spontaneous autoimmune encephalomyelitis.
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-gamma-producing T cells into the CNS takes place approximately 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-gamma-producing CD4(+) T cell into the CNS.
Furtado
Gláucia C
GC
Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, New York, NY 10016, USA.
Marcondes
Maria Cecilia G
MC
Latkowski
Jo-Ann
JA
Tsai
Julia
J
Wensky
Allen
A
Lafaille
Juan J
JJ
D000818:Animals; D015415:Biomarkers / Q000134:cerebrospinal fluid; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000235:genetics / Q000276:immunology*; D002478:Cells, Cultured; D002490:Central Nervous System / Q000276:immunology* / Q000473:pathology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics / Q000276:immunology* / Q000473:pathology* / Q000601:surgery; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D008197:Lymph Node Excision; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000601:surgery; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000276:immunology*; D013997:Time Factors; D015854:Up-Regulation / Q000235:genetics / Q000276:immunology
D015415:Biomarkers; D018984:Epitopes, T-Lymphocyte; D004676:Myelin Basic Protein
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