Autoantigen-pulsed dendritic cells constitute a beneficial cytokine and growth factor network in ameliorating experimental allergic encephalomyelitis

Abstract

Injection of myelin basic protein (MBP)-pulsed dendritic cells (DC) into healthy rats, as we reported before and observed in this study, did not induce clinical experimental allergic encephalomyelitis (EAE), but effectively protected the rats from subsequent EAE induction. The mechanisms by which MBP-pulsed DC mediate immune protection are not completely understood. In the present study, we mainly explored the dynamic change of cytokine and growth factor mRNA expression in spinal cords after subcutaneous injection of MBP-pulsed and unpulsed DC. The expression of interleukin (IL)-1, interferon-gamma and tumour necrosis factor-alpha as well as programmed death ligand (PDL)-1, PDL-2, signal transducer and activator of transcription (STAT)4, STAT6, matrix metalloproteinase (MMP)-9 and tissue inhibitor of metalloproteinases (TIMP)-2 was increased on day 0 postimmunization (p.i.). The increase of IL-12 expression was observed on day 7 p.i., while the increase of IL-10 expression mainly occurred on day 14 p.i. Except downregulation of insulin-like growth factor-1, the expression of brain-derived neurotrophic factor, ciliary neurotrophic factor, fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-B/C as well as nerve growth factor receptor (NGF-R), FGF receptor, PDGF-R-alpha and beta was elevated on day 0 p.i., while the increase of TIMP and NGF was observed on days 0 and 7 p.i. There were no significant differences on MMP-2, spinal cord-derived growth factor and PDGF-A mRNA expression. In line with the suppression of EAE induced by MBP-pulsed DC, the dynamic change of cytokines and growth factors in spinal cords should constitute a beneficial microenvironment against EAE.

Up‐regulation of platelet‐derived growth factor by peripheral‐blood leukocytes during experimental allergic encephalomyelitis

“…PDGFR‐α up‐regulation was therefore probably related to an increase in PDGFR‐α‐expressing O2A cells, also described in experimental demyelination (Redwine and Armstrong, 1998). Notably, subcutaneous injection of MBP‐pulsed dendritic cells suppressed EAE induction in Lewis rats, which seemed related to the creation of a beneficial growth factor microenvironment that also included PDGF and PDGF receptor up‐regulation in the spinal cord (Liu et al, 2005). In this context, it is of interest that PDGF has been shown to exert immunomodulatory effects on immune cells in vitro, probably by influencing cytokine or MHC expression of antigen‐presenting cells (Acres et al, 1985; Daynes et al, 1991; Wiedmeier et al, 1994).…”

Expressions of Some Neurotrophins and Neurotrophic Cytokines at Site of Spinal Cord Injury in Mice after Vaccination with Dendritic Cells Pulsed with Homogenate Proteins

“…It has been reported that neurotrophic factors, such as BDNF, nerve growth factor, NT-3 and NT-4/5, are produced and continuously released at the site of injury by activated T cells [14,37]. These higher levels of neurotrophic factors in spinal cords also contribute to the tolerance to EAE [38]. …”

Blocking glutamate carboxypeptidase II inhibits glutamate excitotoxicity and regulates immune responses in experimental autoimmune encephalomyelitis

“…Briefly, each rat was injected s.c. in both hind footpads with an emulsion containing 100 lg of guinea-pig myelin basic protein (GMBP) in CFA (5 mgÁmL À1 ). The immunized animals were observed daily for clinical signs of disease up to day 19 p.i., and scored on an arbitrary scale of 0-5 in an increasing severity order as follows: no clinical signs (0), flaccid tail (1), hind limb weakness or abnormal gait (2), complete hind limb paralysis (3), complete hind limb paralysis with forelimb weakness or paralysis (4), and moribund or deceased (5) [32]. dissolved in phosphate-buffered saline (PBS) was injected into each mouse intraperitoneally twice a week from the day of inoculation with MOG until the termination of experiments [33].…”