Phosphoantigen/IL2 Expansion and Differentiation of Vγ2Vδ2 T Cells Increase Resistance to Tuberculosis in Nonhuman Primates

Dominant vγ2vδ2 t-cell subset exist only in primates,and recognize phosphoantigen from selected pathogens including m. tuberculosis(mtb). in vivo function of vγ2vδ2 t cells in tuberculosis remains unknown. we conducted mechanistic studies to determine whether earlier expansion/differentiation of vγ2vδ2 t cells during mtb infection could increase immune resistance to tuberculosis in macaques. phosphoantigen/il-2 administration specifically induced major expansion and pulmonary trafficking/accumulation of phosphoantigen-specific vγ2vδ2 t cells,significantly reduced mtb burdens and attenuated tuberculosis lesions in lung tissues compared to saline/bsa or il-2 controls. expanded vγ2vδ2 t cells differentiated into multifunctional effector subpopulations capable of producing anti-tb cytokines ifnγ,perforin and granulysin,and co-producing perforin/granulysin in lung tissue. mechanistically,perforin/granulysin-producing vγ2vδ2 t cells limited intracellular mtb growth,and macaque granulysin had mtb-bactericidal effect,and inhibited intracellular mtb in presence of perforin. furthermore,phosphoantigen/il2-expanded vγ2vδ2 t effector cells produced il-12,and their expansion/differentiation led to enhanced pulmonary responses of peptide-specific cd4+/cd8+ th1-like cells. these results provide first in vivo evidence implicating that early expansion/differentiation of vγ2vδ2 t effector cells during mtb infection increases resistance to tuberculosis. thus,data support a rationale for conducting further studies of the γδ t-cell-targeted treatment of established tb,which might ultimately help explore single or adjunctive phosphoantigen expansion of vγ2vδ2 t-cell subset as intervention of mdr-tuberculosis or hiv-related tuberculosis. © 2013 chen et al.