Anti‐IL‐16 therapy reduces CD4+ T‐cell infiltration and improves paralysis and histopathology of relapsing EAE

Infiltration of the central nervous system (CNS) by CD4+ Th1 cells precedes onset and relapses of experimental autoimmune encephalomyelitis (EAE). We reported that (B6 × SJL) F1 (H‐2 b/s ) mice with severe relapsing‐remitting disease had extensive infiltration by CD4+ T cells compared to that in C57BL/6 (B6) (H‐2 b ) mice, which developed mild low‐relapsing disease in response to myelin oligodendrocyte peptide 35–55 (MOG 35–55 ). This observation led us to search for mechanisms that specifically regulate trafficking of CD4+ cells in relapsing H‐2 b/s mice. We show that the CD4+ cell chemoattractant cytokine interleukin (IL)‐16 has an important role in regulation of relapsing EAE induced by MOG 35–55 in the (B6 × SJL) F1 (H‐2 b/s ) mice. We found production of IL‐16 in the CNS of mice with EAE. IL‐16 levels in the CNS correlated well with the extent of CD4+ T‐cell and B‐cell infiltration during acute and relapsing disease. Infiltrating CD4+ T cells, B cells, and to a lesser extent CD8+ T cells all contained IL‐16 immunoreactivity. Treatment with neutralizing anti‐IL‐16 antibody successfully reversed paralysis and ameliorated relapsing disease. In treated mice, diminished infiltration by CD4+ T cells, less demyelination, and more sparing of axons was observed. Taken together, our results show an important role for IL‐16 in regulation of relapsing EAE. We describe a novel therapeutic approach to specifically impede CD4+ T cell chemoattraction in EAE based on IL‐16 neutralization. Our findings have high relevance for the development of new therapies for relapsing EAE and potentially MS. © 2005 Wiley‐Liss, Inc.