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Swift Entry of Myelin-Specific T Lymphocytes into the Central Nervous System in Spontaneous Autoimmune Encephalomyelitis¹

Gláucia C. Furtado^2,*, Maria Cecilia G. Marcondes^3,*, Jo-Ann Latkowski^*, Julia Tsai^*, Allen Wensky^4,* and Juan J. Lafaille^5,*,

^* Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine of the Skirball Institute and Department of Pathology, New York University School of Medicine, New York, NY 10016

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--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--producing CD4⁺ T cell into the CNS.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported in part by the National Multiple Sclerosis Society (RG3361) and the National Institutes of Health/National Institute of Allergy and Infectious Diseases (AI41647) to J.J.L. and by the National Multiple Sclerosis Society (G3479-A) and The Dana Foundation to G.C.F.

² Current address: Immunology Institute, Mount Sinai School of Medicine, New York, NY 10029.

³ Current address: Department of Molecular and Integrative Neurosciences, The Scripps Research Institute, La Jolla, CA 92037.

⁴ Current address: Department of Molecular Cell Biology and Cancer Research Laboratory, University of California, Berkeley, CA 94720.

⁵ Address correspondence and reprint requests to Dr. Juan J. Lafaille, Molecular Pathogenesis Program, Kimmel Center for Biology and Medicine of the Skirball Institute, New York University School of Medicine, 540 First Avenue, New York, NY 10016. E-mail address: lafaille{at}saturn.med.nyu.edu

⁶ Abbreviations used in this paper: BBB, blood-brain barrier; EAE, experimental autoimmune encephalomyelitis; dcLN, deep cervical lymph nodes; PA, para-aortic; MBP, myelin basic protein.

This article has been cited by other articles:

				H. Zhang, J. R. Podojil, X. Luo, and S. D. Miller Intrinsic and Induced Regulation of the Age-Associated Onset of Spontaneous Experimental Autoimmune Encephalomyelitis J. Immunol., October 1, 2008; 181(7): 4638 - 4647. [Abstract] [Full Text] [PDF]