Differential expression of neurotrophic factors and inflammatory cytokines by myelin basic protein-specific and other recruited T cells infiltrating the central nervous system during experimental autoimmune encephalomyelitis

Abstract

Recent evidence suggests that autoimmune reactions in the central nervous system (CNS) not only have detrimental consequences but can also be neuroprotective, and that this effect is mediated by the expression of neuronal growth factors by infiltrating leucocytes. Here we dissect these two phenomena in guinea pig myelin basic protein peptide (gpMBP 63-88)-induced experimental autoimmune encephalomyelitis (EAE) in the Lewis rat. Real-time TaqMan polymerase chain reaction (PCR) was used to measure mRNA for the nerve growth factors, brain-derived neurotrophic factor (BDNF) and neurotrophin (NT)-3. As reference, the well-known proinflammatory mediator molecules interferon (IFN)-γ and tumour necrosis factor (TNF)-α were quantified. In whole lumbar cord tissue, both the nerve growth factors and the proinflammatory cytokines, IFN-γ and TNF-α, displayed similar expression patterns, peaking at the height of the disease. Among the infiltrating inflammatory cells isolated and sorted from the CNS, αβ+/T-cell receptor (TCR)BV8S2+, but not αβ+/TCRBV8S2-, recognized the encephalitogenic MBP peptide. Interestingly, these two populations displayed contrasting expression patterns of nerve growth factors and proinflammatory cytokines with higher inflammatory cytokine mRNA levels in αβ+/TCRBV8S2+ cells at all time intervals, whereas the levels of BDNF and NT3 were higher in αβ+/TCRBV8S2- cells. We conclude that a potentially important neuroprotective facet of CNS inflammation dominantly prevails within other non-MBP peptide-specific lymphoid cells and that there are independent regulatory mechanisms for neurotrophin and inflammatory cytokine expression during EAE.