Mechanisms of recovery from experimental autoimmune encephalomyelitis: T cell deletion and immune deviation in myelin basic protein T cell receptor transgenic mice.
Experimental autoimmune encephalomyelitis (EAE) is a Th1-type cell-mediated autoimmune disease directed against central nervous system (CNS) myelin antigens such as myelin basic protein (MBP). EaE is usually characterized by spontaneous remission of clinical disease and immune pathology despite the persistence of self myelin antigens in the central nervous system. Following induction of an acute episode of EAE, spontaneous remission also occurs in MBP T cell receptor (TCR) transgenic mice even through most T cells express a TCT specific for MBP. To investigate the mechanisms of recovery associated with EAE, we examined the behavior of MBP-specific T cells in the MBP TCR transgenic mouse model during disease progression and recovery. We found that recovery from EAE was associated with three major immunologic changes: (1) deletion of encephalitogenic T cells in the brain; (2) deviation of MBP-specific transgenic (Tg+) T cells both in the periphery and in the central nervous system from INF- gamma secretin Th1 type cells to cells that secrete IL-4, IL-10, and TGF- beta ; and (3) deletion of Tg+ T cells in the thymus through apoptosis. Thus spontaneous recovery from a classic Th1 type organ specific autoimmune disease is associated with two mechanisms of immune tolerance, deletion of autoreactive cells and immune deviation of autoreactive cells to a non-pathogenic phenotype.
Chen
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Y
Center for Neurological Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, MA 02115, USA.
Hancock
W W
WW
Marks
R
R
Gonnella
P
P
Weiner
H L
HL
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000276:immunology / Q000473:pathology; D002452:Cell Count; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000473:pathology / Q000503:physiopathology*; D007107:Immune System / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic / Q000235:genetics*; D004676:Myelin Basic Protein / Q000235:genetics*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012075:Remission, Spontaneous; D013154:Spleen / Q000276:immunology; D013601:T-Lymphocytes / Q000473:pathology* / Q000502:physiology; D013950:Thymus Gland / Q000473:pathology
D004676:Myelin Basic Protein; D011948:Receptors, Antigen, T-Cell