Antigen presentation in autoimmunity and CNS inflammation: how T lymphocytes recognize the brain.
The central nervous system (CNS) is traditionally viewed as an immune privileged site in which overzealous immune cells are prevented from doing irreparable damage. It was believed that immune responses occurring within the CNS could potentially do more damage than the initial pathogenic insult itself. However, virtually every aspect of CNS tissue damage, including degeneration, tumors, infection, and of course autoimmunity, involves a significant cellular inflammatory component. While the blood-brain barrier (BBB) inhibits diffusion of hydrophilic (immune) molecules across brain capillaries, activated lymphocytes readily pass the endothelial layer of postcapillary venules without difficulty. In classic neuro-immune diseases such as multiple sclerosis or acute disseminated encephalomyelitis, it is thought that neuroantigen-reactive lymphocytes, which have escaped immune tolerance, now invade the CNS and are responsible for tissue damage, demyelination, and axonal degeneration. The developed animal model for these disorders, experimental autoimmune encephalomyelitis (EAE), reflects many aspects of the human conditions. Studies in EAE proved that auto-reactive encephalitogenic T helper (Th) cells are responsible for the onset of the disease. Th cells recognize their cognate antigen (Ag) only when presented by professional Ag-presenting cells in the context of major histocompatibility complex class II molecules. The apparent target structures of EAE immunity are myelinating oligodendrocytes, which are not capable of presenting Ag to invading encephalitogenic T cells. A compulsory third party is thus required to mediate between the attacking T cells and the myelin-expressing target. This review will discuss the recent advances in this field of research and we will discuss the journey of an auto-reactive T cell from its site of activation into perivascular spaces and further into the target tissue.
Becher
Burkhard
B
Neurology Department, Division for Neuroimmunology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. burkhard.becher@neuroimm.unizh.ch
Bechmann
Ingo
I
Greter
Melanie
M
D000818:Animals; D017951:Antigen Presentation / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology*; D001921:Brain / Q000098:blood supply / Q000276:immunology* / Q000473:pathology; D002490:Central Nervous System / Q000098:blood supply / Q000276:immunology* / Q000473:pathology*; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000276:immunology*