A pathogenic role for γ δ T cells in relapsing-remitting experimental allergic encephalomyelitis in the SJL mouse

Abstract

Previous studies have detected γ δ T cells in multiple sclerosis and experimental allergic encephalomyelitis (EAE) lesions but their role remains obscure. In the present study, we assessed γ δ T cell dynamics and distribution in spleen and central nervous system (CNS) from mice with relapsing-remitting EAE, and studied the effect of depleting these cells on clinical and pathologic expression of disease using the mAb GL3. By immunohistochemistry and FACS analysis, striking disease-related changes were observed in the γ δ T cell population in the CNS. FACS analysis showed that while γ δ T cells remained low in the spleen (approximately 2% total CD3+ T cells) at all stages, in the CNS they increased to approximately 12% at the height of the acute attack, fell to approximately 5% during the recovery phase, but rose again to approximately 12% during the chronic phase. In animals in which γ δ T cells were depleted immediately before the onset of acute disease, or during the chronic stage, a striking and significant reduction in the severity of the clinical signs was observed that was associated with a decrease in the percentage of CD3+/γ δ T cells in the CNS. In depleted animals a statistically significant reduction in inflammation and demyelination was noted during the acute stage, but only marginal effects on these disease parameters were found in the chronic phase. Taken together, the data support the conclusion that γ δ T cells play an important role in the pathogenesis of EAE in mice during both acute and chronic/progressive phases of the disease process.