Pertussis Toxin Inhibits Encephalitogenic T-Cell Infiltration and Promotes a B-Cell-Driven Disease during Th17-EAE

Pertussis toxin (PTX) is a required co-adjuvant for experimental autoimmune encephalomyelitis (EAE) induced by immunization with myelin antigen. However, PTX's effects on EAE induced by the transfer of myelin-specific T helper cells is not known. Therefore, we investigated how PTX affects the Th17 transfer EAE model (Th17-EAE). We found that PTX significantly reduced Th17-EAE by inhibiting chemokine-receptor-dependent trafficking of Th17 cells. Strikingly, PTX also promoted the accumulation of B cells in the CNS, suggesting that PTX alters the disease toward a B-cell-dependent pathology. To determine the role of B cells, we compared the effects of PTX on Th17-EAE in wild-type (WT) and B-cell-deficient (mu MT) mice. Without PTX treatment, disease severity was equivalent between WT and mu MT mice. In contrast, with PTX treatment, the mu MT mice had significantly less disease and a reduction in pathogenic Th17 cells in the CNS compared to the WT mice. In conclusion, this study shows that PTX inhibits the migration of pathogenic Th17 cells, while promoting the accumulation of pathogenic B cells in the CNS during Th17-EAE. These data provide useful methodological information for adoptive-transfer Th17-EAE and, furthermore, describe another important experimental system to study the pathogenic mechanisms of B cells in multiple sclerosis.

Automated summary

The study showed that pertussis toxin (PTX) significantly reduced Th17-EAE by inhibiting chemokine-receptor-dependent trafficking of Th17 cells and promoting the accumulation of B cells in the central nervous system. The data suggest that PTX inhibits the migration of pathogenic Th17 cells while promoting the accumulation of pathogenic B cells during Th17-EAE, providing useful information for adoptive-transfer Th17-EAE and studying the pathogenic mechanisms of B cells in multiple sclerosis.