Immunization of V?2V?2 T cells programs sustained effector memory responses that control tuberculosis in nonhuman primates.

ABSTRACT: Tuberculosis (TB) remains a leading killer among infectious diseases, and a better TB vaccine is urgently needed. The critical components and mechanisms of vaccine-induced protection against Mycobacterium tuberculosis (Mtb) remain incompletely defined. Our previous studies demonstrate that V?2V?2 T cells specific for (E)-4-hydroxy-3-methyl-but-2-enyl pyrophosphate (HMBPP) phosphoantigen are unique in primates as multifunctional effectors of immune protection against TB infection. Here, we selectively immunized V?2V?2 T cells and assessed the effect on infection in a rhesus TB model. A single respiratory vaccination of macaques with an HMBPP-producing attenuated Listeria monocytogenes (Lm ?actA prfA*) caused prolonged expansion of HMBPP-specific V?2V?2 T cells in circulating and pulmonary compartments. This did not occur in animals similarly immunized with an Lm ?gcpE strain, which did not produce HMBPP. Lm ?actA prfA* vaccination elicited increases in Th1-like V?2V?2 T cells in the airway, and induced containment of TB infection after pulmonary challenge. The selective immunization of V?2V?2 T cells reduced lung pathology and mycobacterial dissemination to extrapulmonary organs. Vaccine effects coincided with the fast-acting memory-like response of Th1-like V?2V?2 T cells and tissue-resident V?2V?2 effector T cells that produced both IFN-? and perforin and inhibited intracellular Mtb growth. Furthermore, selective immunization of V?2V?2 T cells enabled CD4+ and CD8+ T cells to mount earlier pulmonary Th1 responses to TB challenge. Our findings show that selective immunization of V?2V?2 T cells can elicit fast-acting and durable memory-like responses that amplify responses of other T cell subsets, and provide an approach to creating more effective TB vaccines.

SUBMITTER: Shen L 

PROVIDER: S-EPMC6442559 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature