Autoreactive T cells induce neurotrophin production by immune and neural cells in injured rat optic nerve: implications for protective autoimmunity.
Accumulating evidence suggests that activation of the immune system in the central nervous system (CNS) after trauma protects the CNS from damage propagation and facilitates regeneration. Studies by our group have shown that passive transfer of autoimmune T cells specific to myelin basic protein (T(MBP)) can protect injured neurons in the rat CNS from secondary degeneration. In this study, we investigated the effects of T(MBP) treatment on the local immune response (by B cells and macrophages) and on the expression of neurotrophic factors after crush injury of the rat optic nerve. Systemic injection of activated T(MBP) caused an increase in the accumulation of macrophages/microglia and B cells in the injured nerve, which was greater than that seen in the injured optic nerves of untreated animals. This accumulation was accompanied by a transient, but massive, increase in the expression of neurotrophic factors. Immunocytochemical analysis demonstrated differential expression of neurotrophins by resident astrocytes and by infiltrating B cells, T cells, and macrophages. Because postinjury neuronal survival and maintenance are known to be affected by neurotrophins, our findings point to a possible contribution of a neurotrophin-related mechanism to the protective effect conferred by T cell-mediated autoimmunity on injured neurons.
Barouch
Rina
R
Department of Neurobiology, The Weizmann Institute of Science, Rehovot, Israel.
Schwartz
Michal
M
D000818:Animals; D015551:Autoimmunity; D001402:B-Lymphocytes / Q000276:immunology; D002465:Cell Movement; D005260:Female; D007700:Kinetics; D008264:Macrophages / Q000502:physiology; D017628:Microglia / Q000502:physiology; D018448:Models, Immunological; D004676:Myelin Basic Protein / Q000276:immunology*; D009409:Nerve Crush; D009414:Nerve Growth Factors / Q000032:analysis / Q000096:biosynthesis*; D015213:Neuroimmunomodulation; D009900:Optic Nerve / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D051381:Rats; D011917:Rats, Inbred Lew; D013601:T-Lymphocytes / Q000276:immunology* / Q000637:transplantation
D004676:Myelin Basic Protein; D009414:Nerve Growth Factors