Blood-borne soluble protein antigen intensifies T cell activation in autoimmune CNS lesions and exacerbates clinical disease
- 20 November 2007
- journal article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences
- Vol. 104 (47), 18625-18630
- https://doi.org/10.1073/pnas.0705033104
Abstract
We explored the effect of i.v. soluble antigen on autoaggressive, myelin basic protein-specific effector T cells within their target organ during acute experimental autoimmune encephalomyelitis (EAE). Intravital two-photon imaging revealed that i.v. autoantigen reached the CNS and was taken up and processed by antigen-presenting cells within 30 min after injection. The exogenous autoantigen dramatically changed the motility and function of autoreactive effector T cells within the EAE lesions: T cells that had been cruising through the tissue slowed down and became tethered to local antigen-presenting cells within 1 h. One hour later, the effector T cells massively produced proinflammatory cytokines and up-regulated membranous activation markers. This strong activation of the T cells boosted CNS inflammation and aggravated clinical disease. Postactivated effector and resting memory T cells specific for a non-CNS antigen (ovalbumin) were recruited to EAE lesions and moved there without contacting antigen-presenting cells. These cells were similarly arrested and activated after i.v. infusion of ovalbumin, and they also exacerbated clinical disease. Our data are relevant for autoantigen-based therapies of autoimmune disorders. Further, the study indicates how brain unrelated antigens (microbial components) leaking into the chronically inflamed CNS through the bloodstream might trigger relapses in multiple sclerosis.Keywords
This publication has 34 references indexed in Scilit:
- Instant effect of soluble antigen on effector T cells in peripheral immune organs during immunotherapy of autoimmune encephalomyelitisProceedings of the National Academy of Sciences, 2007
- The Conduit System Transports Soluble Antigens from the Afferent Lymph to Resident Dendritic Cells in the T Cell Area of the Lymph NodeImmunity, 2005
- The blood–brain barrier: an overviewNeurobiology of Disease, 2004
- Loss of Functional Suppression by CD4+CD25+ Regulatory T Cells in Patients with Multiple SclerosisThe Journal of Experimental Medicine, 2004
- The Activation Status of Neuroantigen-specific T Cells in the Target Organ Determines the Clinical Outcome of Autoimmune EncephalomyelitisThe Journal of Experimental Medicine, 2004
- A Conduit System Distributes Chemokines and Small Blood-borne Molecules through the Splenic White PulpThe Journal of Experimental Medicine, 2003
- Antigen-Induced Programmed T Cell Death as a New Approach to Immune TherapyClinical Immunology and Immunopathology, 1995
- Perivascular Microglial Cells of the CNS Are Bone Marrow-Derived and Present Antigen in VivoScience, 1988
- Transfer of experimental allergic encephalomyelitis to bone marrow chimeras. Endothelial cells are not a restricting element.The Journal of Experimental Medicine, 1987
- Molecular mimicry and autoimmune diseaseCell, 1987