Differentiation of human γδ T cells towards distinct memory phenotypes

Vγ9/Vδ2 T cells comprise a small population of peripheral T cells responding towards the low molecular weight antigen, (E)-4-hydroxy-3-methyl-but-2-enyl-pyrophosphate (HMB-PP). HMB-PP-stimulated Vγ9/Vδ2 T cells proliferated, expressed CCL5/RANTES, and upregulated markers like CD16, CD25, CD69, and CD94, in the presence of either IL-15 or IL-21. Vγ9/Vδ2 T cells grown in the presence of IL-15 differentiated into an effector/memory population characterized by production of TNF-α, expression of CD45RO and CCR5, and lack of CD62L, CD81, and CCR7. In contrast, Vγ9/Vδ2 T cells grown with IL-21 differentiated into putative central memory CD45RO+ T cells that did not produce TNF-α, IFN-γ, or IL-4, and maintained expression of CD62L, CD81, and CCR7.