Central nervous system and non-central nervous system antigen vaccines exacerbate neuropathology caused by nerve injury.
Previously, we showed that autoimmune (central nervous system myelin-reactive) T cells exacerbate tissue damage and impair neurological recovery after spinal cord injury. Conversely, independent studies have shown T cell-mediated neuroprotection after spinal cord injury or facial nerve axotomy (FNAx). The antigen specificity of the neuroprotective T cells has not been investigated after FNAx. Here, we compared the neuroprotective capacity of autoimmune and non-autoimmune lymphocytes after FNAx. Prior to axotomy, C57BL/6 mice were immunized with myelin basic protein, myelin oligodendrocyte glycoprotein (MOG) or ovalbumin (a non-self antigen) emulsified in complete Freund's adjuvant (CFA). FNAx mice receiving injections of phosphate-buffered saline (PBS) only (unimmunized) or PBS/CFA emulsions served as controls. At 4 weeks after axotomy, bilateral facial motor neuron counts were obtained throughout the facial motor nucleus using unbiased stereology (optical fractionator). The data show that neuroantigen immunizations and 'generic' lymphocyte activation (e.g. PBS/CFA or ovalbumin/CFA immunizations) exacerbated neuron loss above that caused by FNAx alone. We also found that nerve injury potentiated the effector potential of autoimmune lymphocytes. Indeed, prominent forelimb and hindlimb motor deficits were accompanied by disseminated neuroinflammation and demyelination in FNAx mice receiving subencephalitogenic immunization with MOG. FNAx or neuroantigen (MOG or myelin basic protein) immunization alone did not cause these pathological changes. Thus, irrespective of the antigens used to trigger an immune response, neuropathology was enhanced when the immune system was primed in parallel with nerve injury. These data have important implications for therapeutic vaccination in clinical neurotrauma and neurodegeneration.
Ankeny
Daniel P
DP
Department of Molecular Virology, Immunology & Medical Genetics, The Center for Brain and Spinal Cord Repair and The Institute for Behavioral Medicine Research, The Ohio State University College of Medicine, Columbus, OH, USA.
Popovich
Phillip G
PG
D000818:Animals; D000941:Antigens / Q000276:immunology*; D019771:Axotomy; D002490:Central Nervous System / Q000276:immunology / Q000473:pathology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000473:pathology; D005154:Facial Nerve / Q000166:cytology / Q000473:pathology / Q000601:surgery; D005260:Female; D005620:Freund's Adjuvant; D008213:Lymphocyte Activation; D051379:Mice; D008810:Mice, Inbred C57BL; D017628:Microglia / Q000378:metabolism; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D017933:Peripheral Nervous System / Q000276:immunology / Q000473:pathology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology; D020196:Trauma, Nervous System / Q000276:immunology / Q000473:pathology; D014612:Vaccines / Q000276:immunology*
D000941:Antigens; C571327:Mog protein, mouse; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D014612:Vaccines; D005620:Freund's Adjuvant