期刊
JOURNAL OF NEUROSCIENCE RESEARCH
卷 91, 期 10, 页码 1280-1291出版社
WILEY
DOI: 10.1002/jnr.23257
关键词
CD4(+) T cells; type 2 T helper cells; axonal sprouting; spinal cord injury; neurotrophin-3; Wallerian degeneration; neuroimmune response
资金
- Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Rehabilitation Research and Development
- Christopher and Dana Reeve Foundation
- Mission Connect, a project of the TIRR Foundation
- Craig H. Neilsen Foundation
- NIH [NIAID P30AI036211, NCI P30CA125123]
- NCRR [S10RR024574]
Lesions of the spinal cord cause two distinctive types of neuroimmune responses, a response at the lesion site that leads to additional tissue destruction and a more subtle response, termed Wallerian degeneration (WD), that occurs distal to the lesion site. We have evidence that the neuroimmune response associated with WD may support tissue repair. Previously, we found that overexpression of neurotrophin-3 (NT-3) induced axonal growth in the spinal cord after a unilateral corticospinal tract (CST) lesion, but only if the immune system was intact and activated. We reasoned that a neuroimmune response associated with WD was involved in this neuroplasticity. To test this, we compared NT-3-induced axonal sprouting in athymic nude rats that lack functional T cells with rats with functional T cells and in nude rats grafted with CD4(+) T cells or CD8(+) T cells. There was no sprouting in nude rats and in nude rats grafted with CD8(+) T cells. However, nude rats grafted with CD4(+) T cells mounted a sprouting response. To determine which CD4(+) subtype, type 1 T helper (Th1) or type 2 T helper (Th2) cells, was responsible, we grafted Th1 and Th2 cells into nude rats and tested whether they would support sprouting. Axonal sprouting was greater in rats grafted with Th2 cells, demonstrating that the Th2 subtype was responsible for supporting axonal sprouting. These data suggest that WD activates Th2 cells that, along with the direct effects of NT-3 on CST axons, act to support axonal sprouting in the lesioned spinal cord. (c) 2013 Wiley Periodicals, Inc.
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