Myelin specific Th1 cells are necessary for post-traumatic protective autoimmunity.
Myelin-specific encephalitogenic T cells, when passively transferred into rats or mice, cause an experimental autoimmune disease. Previous studies by our group have shown that (a) the same cells also significantly reduce post-traumatic degeneration in these animals after injury to the central nervous system, (b) this beneficial autoimmunity is a physiological response, and (c) animals differ in their ability to resist injurious conditions, and the ability to resist post-traumatic degeneration correlates with resistance to the development of an autoimmune disease. Here we show that optic nerve neurons in both resistant and susceptible rat strains can be protected from secondary degeneration after crush injury by immunization with myelin basic protein emulsified in complete or incomplete Freund's adjuvant. We provide evidence that potentially destructive autoimmunity (causing autoimmune disease) and beneficial autoimmunity (causing improved neuronal survival) both result from activity of the same myelin-specific, proinflammatory Th1 cells. We further show that following passive transfer of such Th1 cells, the expression of their beneficial potential depends on the activity of an additional T cell (CD4(+)) population. By identifying the additional cellular component of autoimmune neuroprotection, we may be able to take meaningful steps toward achieving neuroprotection without risk of accompanying autoimmune disease.
Kipnis
Jonathan
J
Department of Neurobiology, The Weizmann Institute of Science, 76100, Rehovot, Israel.
Mizrahi
Tal
T
Yoles
Eti
E
Ben-Nun
Avraham
A
Schwartz
Michal
M
Ben-Nur
Auraham
A
D000818:Animals; D015551:Autoimmunity / Q000276:immunology*; D001930:Brain Injuries / Q000276:immunology* / Q000503:physiopathology / Q000628:therapy; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002470:Cell Survival / Q000276:immunology* / Q000528:radiation effects; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins / Q000276:immunology*; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D014611:Vaccination / Q000379:methods; D014965:X-Rays / Q000009:adverse effects
D004676:Myelin Basic Protein; D009185:Myelin Proteins