TY - JOUR
T1 - Adoptive transfer of phosphoantigen-specific γδ T cell subset attenuates mycobacterium tuberculosis infection in nonhuman primates
AU - Qaqish, Arwa
AU - Huang, Dan
AU - Chen, Crystal Y.
AU - Zhang, Zhuoran
AU - Wang, Richard
AU - Li, Shengpu
AU - Yang, Enzhuoa
AU - Lu, Yang
AU - Larsen, Michelle H.
AU - Jacobs, William R.
AU - Qian, Lixia
AU - Frencher, James
AU - Shen, Ling
AU - Chen, Zheng W.
N1 - Funding Information:
This work was supported by National Institutes of Health Grants R010D015092, R01HL64560, and R01HL129887.
PY - 2017/6/15
Y1 - 2017/6/15
N2 - The dominant Vγ2Vγ2 T cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. Despite the discovery of γ δ T cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the Vγ2Vδ2 T cell subset is protective against Mycobacterium tuberculosis and other infections. In this study, we used an adoptive cell-transfer strategy to define the protective role of Vγ2Vδ2 T cells in a primate tuberculosis (TB) model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions, including the production of anti-M. tuberculosis cytokines and inhibition of intracellular mycobacteria. They also expressed CXCR3/CCR5/LFA-1 trafficking/tissue-resident phenotypes and consistently trafficked to the airway, where they remained detectable from 6 h through 7 d after adoptive transfer. Interestingly, the test group of macaques receiving transfer of Vγ2Vδ2 T cells at weeks 1 and 3 after high-dose (500 CFU) M. tuberculosis infection exhibited significantly lower levels of M. tuberculosis infection burdens in lung lobes and extrapulmonary organs than did the control groups receiving PBLs or saline. Consistently, adoptive transfer of Vγ2Vδ2 T cells attenuated TB pathology and contained lesions primarily in the infection site of the right caudal lung lobe, with no or reduced TB dissemination to other lobes, spleen, or liver/kidney; in contrast, the controls showed widespread TB dissemination. The proof-of-concept finding supports the view that the dominant Vγ2Vγ2 T cell subset may be included in the rational design of a TB vaccine or host-directed therapy.
AB - The dominant Vγ2Vγ2 T cell subset recognizes phosphoantigen and exists only in humans and nonhuman primates. Despite the discovery of γ δ T cells >30 y ago, a proof-of-concept study has not been done to prove the principle that the Vγ2Vδ2 T cell subset is protective against Mycobacterium tuberculosis and other infections. In this study, we used an adoptive cell-transfer strategy to define the protective role of Vγ2Vδ2 T cells in a primate tuberculosis (TB) model. Vγ2Vδ2 T cells for adoptive transfer displayed central/effector memory and mounted effector functions, including the production of anti-M. tuberculosis cytokines and inhibition of intracellular mycobacteria. They also expressed CXCR3/CCR5/LFA-1 trafficking/tissue-resident phenotypes and consistently trafficked to the airway, where they remained detectable from 6 h through 7 d after adoptive transfer. Interestingly, the test group of macaques receiving transfer of Vγ2Vδ2 T cells at weeks 1 and 3 after high-dose (500 CFU) M. tuberculosis infection exhibited significantly lower levels of M. tuberculosis infection burdens in lung lobes and extrapulmonary organs than did the control groups receiving PBLs or saline. Consistently, adoptive transfer of Vγ2Vδ2 T cells attenuated TB pathology and contained lesions primarily in the infection site of the right caudal lung lobe, with no or reduced TB dissemination to other lobes, spleen, or liver/kidney; in contrast, the controls showed widespread TB dissemination. The proof-of-concept finding supports the view that the dominant Vγ2Vγ2 T cell subset may be included in the rational design of a TB vaccine or host-directed therapy.
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U2 - 10.4049/jimmunol.1602019
DO - 10.4049/jimmunol.1602019
M3 - Article
C2 - 28526681
AN - SCOPUS:85020382379
VL - 198
SP - 4753
EP - 4763
JO - Journal of Immunology
JF - Journal of Immunology
SN - 0022-1767
IS - 12
ER -