Reduced chemokine and chemokine receptor expression in spinal cords of TCR BV8S2 transgenic mice protected against experimental autoimmune encephalomyelitis with BV8S2 protein.
The perivascular transmigration and accumulation of macrophages and T lymphocytes in the CNS of mice with experimental autoimmune encephalomyelitis (EAE) may be partly regulated by low m.w. chemotactic cytokines. Using the RNase protection assay and ELISA, we quantified expression of chemokines and chemokine receptors in the spinal cord (SC), brain, and lymph nodes of BV8S2 transgenic mice that developed or were protected from EAE by vaccination with BV8S2 protein. In paralyzed control mice, the SC had increased cellular infiltration and strong expression of the chemokines RANTES, IFN-inducible 10-kDa protein, and monocyte chemoattractant protein-1 and the cognate chemokine receptors CCR1, CCR2, and CCR5, with lower expression of macrophage-inflammatory protein (MIP)-1alpha, MIP-1beta, and MIP-2; whereas brain had less infiltration and a lower expression of a different pattern of chemokines and receptors. In TCR-protected mice, there was a decrease in the number of inflammatory cells in both SC and brain. In SC, the reduced cellular infiltrate afforded by TCR vaccination was commensurate with profoundly reduced expression of chemokines and their cognate chemokine receptors. In brain, however, TCR vaccination did not produce significant changes in chemokine expression but resulted in an increased expression of CCR3 and CCR4 usually associated with Th2 cells. In contrast to CNS, lymph nodes of protected mice had a significant increase in expression of MIP-2 and MIP-1beta but no change in expression of chemokine receptors. These results demonstrate that TCR vaccination results in selective reduction of inflammatory chemokines and chemokine receptors in SC, the target organ most affected during EAE.
Matejuk
A
A
Department of Neurology and Molecular Microbiology, Oregon Health Sciences University, Portland, OR 97201, USA. matejuka@ohsu.edu
Vandenbark
A A
AA
Burrows
G G
GG
Bebo
B F
BF
Offner
H
H
D000818:Animals; D001921:Brain / Q000276:immunology / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D018925:Chemokines / Q000096:biosynthesis* / Q000378:metabolism; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism / Q000517:prevention & control; D005260:Female; D015870:Gene Expression / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics* / Q000276:immunology / Q000378:metabolism / Q000627:therapeutic use*; D019707:Receptors, Chemokine / Q000096:biosynthesis* / Q000235:genetics; D013116:Spinal Cord / Q000276:immunology* / Q000378:metabolism*; D014611:Vaccination
D018925:Chemokines; D016693:Receptors, Antigen, T-Cell, alpha-beta; D019707:Receptors, Chemokine