gamma delta T cells in EAE: Early trafficking events and cytokine requirements

We have previously shown that gamma delta T cells traffic to the CNS during EAE with concurrently increased expression of beta(2)-integrins and production of IFN-gamma and TNF-alpha. To extend these studies, we transferred bioluminescent gamma delta T cells to WT mice and followed their movement through the acute stages of disease. We found that gamma delta T cells rapidly migrated to the site of myelin oligodendrocyte glycoprotein peptide injection and underwent massive expansion. Within 6 days after EAE induction, bioluminescent gamma delta T cells were found in the spinal cord and brain, peaking in number between days 10 and 12 and then rapidly declining by day 15. Reconstitution of gamma delta T cell(-/-) mice with gamma delta T cells derived from beta(2)-integrin-deficient mice (CD11a, -b or -c) demonstrated that gamma delta T-cell trafficking to the CNS during EAE is independent of this family of adhesion molecules. We also examined the role Of 78 T-cell-produced IFN-gamma and TNF-alpha in EAE and found that production of both cytokines by gamma delta T cells was required for full development of EAE. These results indicate that gamma delta T cells are critical for the development of EAE and suggest a therapeutic target in demyelinating disease.