Reduced chemokine and chemokine receptor expression in spinal cords of TCRBV8S2 transgenic mice protected against experimental autoimmune encephalomyelitis with BV8S2 protein

The perivascular transmigration and accumulation of macrophages and T lymph ocytes in the CNS of mice with experimental autoimmune encephalomyelitis (E AE) may be partly regulated by low m.w. chemotactic cytokines, Using the RN ase protection assay and ELISA, we quantified expression of chemokines and chemokine receptors in the spinal cord (SC), brain, and lymph nodes of BV8S 2 transgenic mice that developed or were protected from EAE by vaccination with BV8S2 protein, In paralyzed control mice, the SC had increased cellula r infiltration and strong expression of the chemokines RANTES, IFN-inducibl e 10-kDa protein, and monocyte chemoattractant protein-1 and the cognate ch emokine receptors CCR1, CCR2, and CCR5,with lower expression of macrophage inflammatory protein (MIP)-1 alpha, MIP-1 beta, and MIP-2; whereas brain ha d less infiltration and a lower expression of a different pattern of chemok ines and receptors, In TCR-protected mice, there was a decrease in the numb er of inflammatory cells in both SC and brain. In SC, the reduced cellular infiltrate afforded by TCR vaccination was commensurate with profoundly red uced expression of chemokines and their cognate chemokine receptors, In bra in, however, TCR vaccination did not produce significant changes in chemoki ne expression but resulted in an increased expression of CCR3 and CCR4 usua lly associated with Th2 cells. In contrast to CNS, lymph nodes of protected mice had a significant increase in expression of MIP-2 and MIP-1 beta but no change in expression of chemokine receptors, These results demonstrate t hat TCR vaccination results in selective reduction of inflammatory chemokin es and chemokine receptors in SC, the target organ most affected during EAE .