Autoreactive T cells promote post-traumatic healing in the central nervous system.
In general, autoimmune responses are considered harmful to the host. In the best-defined model of autoimmune disease, murine experimental allergic encephalomyelitis (EAE), for example, brain-protein-specific autoimmune responses of both major classes, type-1 and type-2, have been implicated in causing brain pathology. We induced type-1 and type-2 autoimmunity to myelin oligodendrocyte protein (MOG) in C57.BL/6 mice. Instead of using pertussis toxin (PTX) to open the blood-brain barrier (BBB), which is the classic procedure, we set an aseptic cerebral injury (ACI) to see what the consequences of pre-primed, autoreactive type-1 and type-2 memory T cells gaining access to the brain in the course of sterile tissue injury would be. Neither of these autoimmune response types induced pathology; on the contrary, both accelerated re-vascularization and post-traumatic healing. The data suggest that induction of either type-1 or type-2 autoimmune responses is not inherently noxious to the host, but can have beneficial effects on tissue repair. Autoimmune pathology may develop only if molecules of microbial origin such as pertussis toxin additionally induce the "infectious nonself/danger" reaction in the antigen-presenting cells (APC) of the target organ itself.
Hofstetter
Harald H
HH
Department of Pathology, Case Western Reserve University School of Medicine, 10900 Euclid Avenue, BRB 929, Cleveland OH 44106-4943, USA.
Sewell
Diane L
DL
Liu
Frances
F
Sandor
Matyas
M
Forsthuber
Thomas
T
Lehmann
Paul V
PV
Fabry
Zsuzsa
Z
D000818:Animals; D015551:Autoimmunity / Q000187:drug effects / Q000276:immunology*; D001812:Blood-Brain Barrier / Q000276:immunology*; D001930:Brain Injuries / Q000276:immunology* / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology; D005260:Female; D005620:Freund's Adjuvant / Q000494:pharmacology; D006023:Glycoproteins / Q000276:immunology / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology; D037342:Pertussis Toxin / Q000276:immunology / Q000494:pharmacology; D018417:Th1 Cells / Q000276:immunology*; D018418:Th2 Cells / Q000276:immunology*; D014945:Wound Healing / Q000276:immunology*
D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; C445081:myelin oligodendrocyte glycoprotein (35-55); D005620:Freund's Adjuvant; D037342:Pertussis Toxin