Neuroprotection by encephalomyelitis: Rescue of mechanically injured neurons and neurotrophin production by CNS-infiltrating T and natural killer cells

In experimental autoimmune encephalomyelitis (EAE), CD4(+) self-reactive T cells target myelin components of the CNS. However, the consequences of an autoaggressive T cell response against myelin for neurons are currently unk nown. We herein demonstrate that EAE induced by active immunization with an encephalitogenic myelin basic protein peptide dramatically reduces the los s of spinal motoneurons after ventral root avulsion in rats. Both brain-der ived neurotophic factor (BDNF)- and neurotrophin-3 (NT-3)-like immunoreacti vities were detected in mainly T and natural killer (NK) cells in the spina l cord. In addition, very high levels of BDNF, NT-3, and glial cell line-de rived neurotrophic factor mRNAs were present in T and NK cell populations i nfiltrating the CNS. Interestingly, bystander recruited NK and T cells disp layed similar or higher neurotrophic factor levels compared with the EAE di sease-driving encephalitogenic T cell population. High levels of tumor necr osis factor-alpha (TNF-alpha) and interferon-gamma (IFN-gamma) mRNAs were a lso detected, and both these cytokines can be harmful to several types of C NS cells, including neurons. However, treatment of embryonic motoneuron cul tures with TNF-alpha or IFN-gamma only had a deleterious effect in cultures deprived of neurotrophic factors. These results suggest that the potential ly neurodamaging consequences of severe CNS inflammation are curbed by the production of several potent neurotrophic factors in leukocytes.