Production of Neurotrophins by Activated T Cells: Implications for Neuroprotective Autoimmunity

Department of Neurobiology, The Weizmann Institute of Science, Rehovot, 76100, Israel.
Journal of Autoimmunity (Impact Factor: 7.02). 12/2000; 15(3):331-45. DOI: 10.1006/jaut.2000.0441
Source: PubMed

ABSTRACT Neurotrophins (NTs) promote neuronal survival and maintenance during development and after injury. However, their role in the communication between the nervous system and the immune system is not yet clear. We observed recently that passively transferred activated T cells of various antigen specificities home to the injured central nervous system (CNS), yet only autoimmune T cells specific to a CNS antigen, myelin basic protein (MBP), protect neurons 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 in this activity. Analysis of cytokine and NT expression in various rat T cell lines showed that the T cells express mRNA for cytokines of Th1, Th2, and Th3 phenotypes. In addition, the T cells express mRNA and protein specific to nerve growth factor, brain-derived neurotrophic factor, NT-3, and NT-4/5. Antigen activation significantly increased NT secretion. Thus, reactivation 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 other factors in injured optic nerves. mRNA for TrkA, TrkB and p75 receptors was expressed in the injured nerve, suggesting that these specific receptors can mediate the effects of the T-cell-derived NTs. The neuroprotective effect of the passively transferred autoimmune anti-MBP T cells in injured optic nerves was significantly decreased after local applicaiton of a tyrosine kinase inhibitor known to be associated with NT-receptor activity. These results suggest that the neuroprotective effect of autoimmune T cells involves 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 CNS might prove to be a useful means of promoting post-injury CNS maintenance and recovery, possibly via supply of NTs and other factors.

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Available from: Philip Lazarovici, Aug 23, 2015
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    • "One mechanism proposed for autoimmune lymphocyte-mediated tissue repair is the production of neurotrophins (e.g., brain-derived neurotrophic factor (BDNF)) (Hammarberg et al., 2000; Moalem et al., 2000) and/or anti-inflammatory cytokines (e.g., IL-10, transforming growth factor (TGF)-β) (Tyor et al., 2002; Zhou et al., 2009a). However, the cell type(s) responsible for the production of neurotrophins and anti-inflammatory mediators within the injured CNS, i.e., whether they are effector cells or induced T regs (iTregs) that bind CNS proteins, or even non-antigen-specific bystander cells recruited to the injury site, has not been definitively established. "
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    • "Another mechanism by which A91 immunization could be reducing apoptosis is through the action of BDNF. Previous studies have shown that anti-MBP T cells release neurotrophic factors [38] [39]. Furthermore, anti-A91 T lymphocytes are capable of releasing significant amounts of BDNF [14]. "
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    • "It was further demonstrated that newly born cells in the DG are clustered in close proximity to blood vessels where VEGF expression is usually high, which suggests that the development of newborn cells is strongly influenced by local environmental factors (Palmer et al. 2000). Existing evidence demonstrates that both BDNF (Moalem et al. 2000) and VEGF (Khaibullina et al. 2004) receptors are expressed by T cells (Freeman et al. 1995). These T cell-mediated proneurogenic factors may potentiate the intrinsic capacity of newly born cells to respond to the mitotic stimuli provided by the neurogenic microenvironment. "
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