期刊
ISCIENCE
卷 25, 期 3, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2022.103889
关键词
-
资金
- NIH/NIAID [R01 AI10 2693, R21 AI145642, P51 OD011104]
This study reports the effects of in vivo iNKT activation in Mauritian-origin cynomolgus macaques using a humanized monoclonal antibody, NKTT320. The results show that NKTT320 rapidly activates iNKT, increases its polyfunctionality, and upregulates inflammation-modulating genes. The study suggests that NKTT320 has a sustained effect on iNKT activation and could be used as an immunotherapeutic.
Invariant natural killer T-lymphocytes (iNKT) are unique immunomodulatory innate T cells with an invariant TCRa recognizing glycolipids presented on MHC class-I-like CD1d molecules. Activated iNKT rapidly secrete pro-and anti-inflammatory cytokines, potentiate immunity, and modulate inflammation. Here, we report the effects of in vivo iNKT activation in Mauritian-origin cynomolgus macaques by a humanized monoclonal antibody, NKTT320, that binds to the invariant region of the iNKT TCR. NKTT320 led to rapid iNKT activation, increased polyfunctionality, and elevation of multiple plasma analytes within 24 hours. Flow cytometry and RNA-Seq confirmed downstream activation of multiple immune subsets, enrichment of JAK/STAT and PI3K/AKT pathway genes, and upregulation of inflammation-modulating genes. NKTT320 also increased iNKT frequency in adipose tissue and did not cause iNKT anergy. Our data indicate that NKTT320 has a sustained effect on in vivo iNKT activation, potentiation of innate and adaptive immunity, and resolution of inflammation, which supports its future use as an immunotherapeutic.
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