THE EFFECT OF GAMMA-DELTA T-CELL DEPLETION ON CYTOKINE GENE-EXPRESSION IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS

In experimental autoimmune encephalomyelitis (EAE), a model for multip le sclerosis, we showed previously that depletion of gamma delta T cel ls using the mAb GL3 immediately before disease onset, or during the c hronic phase, significantly ameliorated clinical severity. We now repo rt on the effect of gamma delta T cell depletion on expression of five cytokine genes, IL-1, IL-6, TNF, lymphotoxin, and IFN-gamma in spinal cords of mice during the pre-onset, onset, height, and recovery phase s of EAE, and on expression of type II nitric oxide synthase, In contr ol animals, the mRNAs for IL-1 and IL-6 rose dramatically at disease o nset and peaked before disease height, whereas the mRNAs for TNF, lymp hotoxin, and IFN-gamma rose more slowly and peaked with peak of diseas e, In GL3-treated animals, a dramatic reduction in all five cytokines was noted at disease onset, but only IFN-gamma remained significantly reduced at a time point equivalent to height of disease in control ani mals. ELISA data confirmed the reduced levels of LL-1 and IL-6 at dise ase onset in GL3-treated animals, and pathologic analysis demonstrated a marked reduction in meningeal infiltrates at the same time point, S tudies of type II NOS also demonstrated a significant reduction in bot h mRNA and protein-expression at the height of disease in GL3-treated animals. These results suggest that gamma delta T cells contribute to the pathogenesis of EAE by regulating the influx of inflammatory cells into the spinal cord and by augmenting the proinflammatory cytokine p rofile of the inflammatory infiltrates.