Production of neurotrophins by activated T cells: Implications for neuroprotective autoimmunity

Neurotrophins (NTs) promote neuronal survival and maintenance during develo pment and after injury. However, their role in the communication between th e nervous system and the immune system is not yet clear. We observed recent ly that passively transferred activated T cells of various antigen specific ities home to the injured central nervous system (CNS), yet only autoimmune T cells specific to a CNS antigen, myelin basic protein (MBP), protect neu rons from secondary degeneration after crush injury of the rat optic nerve. Here we examined the involvement of NTs in T-cell-mediated neuroprotection , and the possible significance of the antigen specificity of the T cells i n this activity. Analysis of cytokine and NT expression in various rat T ce ll lines showed that the T cells express mRNA for cytokines of Th1, Th2, an d Th3 phenotypes. in addition, the T cells express mRNA and protein specifi c to nerve growth factor, brain-derived neurotrophic factor, NT-3, and NT-4 /5. Antigen activation significantly increased NT secretion. Thus, reactiva tion of CNS autoimmune T cells by locally presented antigens to which they are specific can lead to enhanced secretion of NTs and possibly also of oth er factors in injured optic nerves. mRNA for TrkA, TrkB and p75 receptors w as expressed in the injured nerve, suggesting that these specific receptors can mediate the effects of the T-cell-derived NTs. The neuroprotective eff ect of the passively transferred autoimmune anti-MBP T cells in injured opt ic nerves was significantly decreased after local applicaiton of a tyrosine kinase inhibitor known to be associated with NT-receptor activity. These r esults suggest that the neuroprotective effect of autoimmune T cells involv es the secretion of factors such as NTs by the T cells reactivated by their specific antigen in the injured CNS. T cell intervention in the injured CN S might prove to be a useful means of promoting post-injury CNS maintenance and recovery, possibly via supply of NTs and other factors. (C) 2000 Acade mic Press.