Phenotypic and functional analysis of gamma delta T cells in the pathogenesis of human T-cell lymphotropic virus type 1 infection

The human T-cell leukemia virus type 1 (HTLV-1) is the cause of serious malignant and inflammatory diseases, including adult T-cell leukemia and lymphoma and tropical spastic paraparesis. The potential protective role of gamma delta T cells in HTLV-1 infection remains unclear. Here, demonstrate that there is a decrease in the amount of V gamma 9V delta 2 T cells in patients with HTLV-1, especially in those with HTLV-1 associated pathologies. This suggests that gamma delta T cells could be involved in controlling the virus. Indeed, we found that V gamma 9V delta 2 T cells, expanded from non-infected individuals, can kill cells expressing the viral proteins HBZ and Tax and this phenotype is reversed in the presence of mevastatin. Cytotoxicity by V gamma 9V delta 2 T cells was not associated with an increase of INF-gamma production. In sharp contrast, killing by NK cells was reduced by Tax expression. Thus, our study provides initial evidence for a potential protective role of V gamma 9V delta 2 T cells against HTLV-1 infection. Therapeutic exploitation of these insights is feasible with current technologies of T-cell therapies and could provide novel tools to prevent and treat HTLV-1-associated malignancies and neurologic complications.