Immunization of Vγ2Vδ2 T cells programs sustained effector memory responses that control tuberculosis in nonhuman primates

作者：Ling Shen, James T. Frencher, Dan Huang, Wandang Wang, Enzhuo Yang, Crystal Y. Chen, Zhuoran Zhang, Richard Wang, Arwa Qaqish, Michelle H. Larsen, Hongbo Shen, Steven Anthony Porcelli, William R. Jacobs, Zheng W. Chen · 发表于：Proceedings of the National Academy of Sciences · 年份：2019 · DOI：10.1073/pnas.1811380116 · 被引用次数：95 · 研究领域：T-cell and B-cell Immunology、Immune Cell Function and Interaction、Immune Response and Inflammation

Significance Despite the urgent need for a better tuberculosis (TB) vaccine, relevant protective mechanisms remain unknown. We previously defined protective phosphoantigen (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP)–specific Vγ2Vδ2 T cells as a unique subset in primates, and, here, we immunized them selectively for protection against TB. A single respiratory vaccination of macaques with attenuated HMBPP-producing Listeria monocytogenes (Lm ΔactA prfA *), but not an HMBPP-lacking ΔgcpE Listeria strain, expanded Vγ2Vδ2 T cells, elicited Th1-like Vγ2Vδ2 T cell responses, and reduced TB infection/pathology after moderate-dose TB challenge. Such protection correlated with rapid memory-like, Th1-like Vγ2Vδ2 T cell responses, the presence of tissue-resident Vγ2Vδ2 T effectors coproducing IFN-γ/perforin and inhibiting intracellular Mycobacterium tuberculosis growth, and enhanced CD4 + /CD8 + T cell responses. These findings establish a concept incorporating immunization of human Vγ2Vδ2 T cells for TB vaccine development.