Expansion, Reexpansion, and Recall-Like Expansion of Vγ2Vδ2 T Cells in Smallpox Vaccination and Monkeypox Virus Infection

Little is known about the in vivo kinetics of T-cell responses in smallpox/monkeypox. We showed that macaque V gamma 2V delta 2 T cells underwent 3-week-long expansion after smallpox vaccine immunization and displayed simple reexpansion in association with sterile anti-monkeypox virus (anti-MPV) immunity after MPV challenge. Virus-activated V gamma 2V delta 2 T cells exhibited gamma interferon-producing effector function after phosphoantigen stimulation. Surprisingly, like alpha beta T cells, suboptimally primed V gamma 2V delta 2 T cells in vaccinia virus/cidofovir-covaccinated macaques mounted major recall-like expansion after MPV challenge. Finally, V gamma 2V delta 2 T cells localized in inflamed lung tissues for potential regulation. Our studies provide the first in vivo evidence that viruses, despite their inability to produce exogenous phosphoantigen, can induce expansion, reexpansion, and recall-like expansion of V gamma 2V delta 2 T cells and stimulate their antimicrobial cytokine response.