Temporal kinetics and cellular phenotype of TNF p55/p75 receptors in experimental allergic encephalomyelitis

TNF-alpha and LT-alpha are thought to be involved in the immunopathology of CNS demyelinating diseases. Both cytokines induce cellular effects through 55-kDa type-1 receptors (R1) and 75-kDa type-2 receptors (R2). To date, no study has specifically identified the various cell populations that expres s TNF receptors (TNFR) in the inflammatory and demyelinating mouse model, E AE. Phenotyping the TNFR positive cells is important in determining when an d where the ligands may be acting and playing a role in disease pathology. We observed an upregulation of TNF RI and R2 mRNA in high endothelial venul es (HEVs) in the lymph node and CNS before the onset of EAE (preclinical ph ase). This upregulation of TNFR expression in HEVs was followed by a rapid increase in leukocytes within the CNS after the onset of clinical disease. The temporal kinetics of these data suggest that HEVs become activated earl y, probably through the release of pro-inflammatory cytokines originating f rom circulating leukocytes. An increase in TNFR on HEVs would make these ce lls more susceptible to TNF-induced changes, such as increasing cellular ad hesion molecules, thereby further facilitating the trafficking of leukocyte s into the CNS parenchyma. (C) 1999 Elsevier Science B.V. All rights reserv ed.