γδ T cells in EAE: Early trafficking events and cytokine requirements

Abstract

We have previously shown that γδ T cells traffic to the CNS during EAE with concurrently increased expression of β₂‐integrins and production of IFN‐γ and TNF‐α. To extend these studies, we transferred bioluminescent γδ T cells to WT mice and followed their movement through the acute stages of disease. We found that γδ T cells rapidly migrated to the site of myelin oligodendrocyte glycoprotein peptide injection and underwent massive expansion. Within 6 days after EAE induction, bioluminescent γδ 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 γδ T cell^−/− mice with γδ T cells derived from β₂‐integrin‐deficient mice (CD11a, ‐b or ‐c) demonstrated that γδ T‐cell trafficking to the CNS during EAE is independent of this family of adhesion molecules. We also examined the role of γδ T‐cell‐produced IFN‐γ and TNF‐α in EAE and found that production of both cytokines by γδ T cells was required for full development of EAE. These results indicate that γδ T cells are critical for the development of EAE and suggest a therapeutic target in demyelinating disease.