Early Preferential Stimulation of γδ T Cells by TNF-α

Abstract

Abstract Although recent findings indicate that γδ T cells influence both early innate and Ag-specific adaptive host responses, it has remained unclear what triggers γδ T cell reactivity. Investigating very early T cell activation in mouse and human models of bacterial infection, we measured CD69 expression as an indicator of early cellular activation. Both murine αβ and γδ T cells responded polyclonally to systemic bacterial infections, and to LPS. However, γδ T cells responded more strongly to the bacteria and to LPS. In vitro LPS-stimulated human T cells showed a similar differential response pattern. We identified TNF-α as mediator of the early differential T cell activation, and of differential proliferative responses. The stronger response of γδ T cells to TNF-α was correlated with higher inducible expression levels of TNF-Rp75. Among unstimulated splenocytes, more γδ T cells than αβ T cells expressed CD44 at high levels. The data suggest that TNF-Rp75 determines the differential T cell reactivity, and that most γδ T cells in the normal spleen are present in a presensitized state. As TNF-α stimulates activated T cells, it may early preferentially connect γδ T cell functions with those of cells that produce this cytokine, including activated innate effector cells and Ag-stimulated T lymphocytes.