Anti-inflammatory activity of nerve growth factor in experimental autoimmune encephalomyelitis: inhibition of monocyte transendothelial migration

In order to analyze a putative immunomodulatory effect of NGF in experiment al autoimmune encephalomyelitis (EAE) of the Lewis rat, we transduced myeli n basic protein (MBP)-specific CD4(+) T cells with a recombinant retrovirus encoding NGF. These T(MBP)NGF cells secreted high levels of NGF, along wit h an unaltered Th1-like cytokine pattern. Transfer studies showed that T(MB P)NGF cells were unable to mediate clinical EAE, when transferred alone, an d, more important, they efficiently suppressed induction of clinical EAE by non-transduced MBP-specific T cells (T-MBP cells). In contrast, NGF transd uced ovalbumin-specific T cells, which secreted high NGF levels, did not af fect EAE induction. Suppression of clinical EAE by T(MBP)NGF cells was asso ciated with a general reduction of inflammatory CNS infiltrates, with a mos t pronounced decrease of the monocyte/macrophage component. Using a culture model of the endothelial blood-brain barrier (BBB), we found that NGF dire ctly acts on blood-derived monocytes via the p75 NGF receptor, thus interfe ring with monocyte migration through the activated BBB endothelium. Our dat a establish NGF as an anti-inflammatory mediator interfering with T cell me diated autoimmune disease in the CNS. They further point to monocyte migrat ion through blood vascular endothelium as one possible mechanism of NGF act ion.