Activated T cells induce proliferation of oligodendrocyte progenitor cells via release of vascular endothelial cell growth factor‐A. Issue 11 (30th November 2018)

• Record Type: Journal Article
• Authors: Choi, Elliot H.; Xu, Yadi; Medynets, Marie; Monaco, Maria Chiara G.; Major, Eugene O.; Nath, Avindra; Wang, Tongguang
• Is Part Of: Glia. Volume 66:Issue 11(2018)
• Page Start: 2503
• Page End: 2513
• Publication Date: 2018-11-30
• Subjects: neural inflammation -- neural stem cells -- oligodendrocyte progenitor cells -- T cells -- VEGF; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.23501
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: Neuroinflammatory diseases such as multiple sclerosis are characterized by infiltration of lymphocytes into the central nervous system followed by demyelination and axonal degeneration. While evidence suggests that activated T lymphocytes induce neurotoxicity and impair function of neural stem cells, the effect of T cells on oligodendrocyte progenitor cells (OPCs) is still uncertain, partly due to the difficulty in obtaining human OPCs. Here we studied the effect of activated T cells on OPCs using OPCs derived from human hematopoietic stem cells or from human fetal brain. OPCs were exposed to supernatants (sups) from activated T cells. Cell proliferation was determined by EdU incorporation and CellQuanti‐Blue assays. Surprisingly, we found that sups from activated T cells induced OPC proliferation by regulating cell cycle progression. Vascular endothelial growth factor A (VEGF‐A) transcripts were increased in T cells after activation. Immunodepletion of VEGF‐A from activated T cell sups significantly attenuated its effect on OPC proliferation. Furthermore, VEGF receptor 2 (VEGFR2) was expressed on OPCs and its inhibition also attenuated activated T cell‐induced OPC proliferation. Thus, activated T cells have a trophic role by promoting OPC proliferation via the VEGFR2 pathway. Main Points: Activated T cells induce OPC proliferation. Activation of T cells produce VEGF‐A Depletion of VEGF‐A attenuates activated T cell‐induced OPC proliferation VEGFR2 inhibition attenuates VEGF‐A induced OPC proliferation.