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20240926232533.0 |
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240729s2024 xx |||||o 00| ||eng c |
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|a 10.1016/j.clim.2024.110331
|2 doi
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|a pubmed24n1549.xml
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|a (DE-627)NLM375551832
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|a (NLM)39067675
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|a (PII)S1521-6616(24)00440-6
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|a DE-627
|b ger
|c DE-627
|e rakwb
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|a eng
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| 100 |
1 |
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|a Ji, Xuejiao
|e verfasserin
|4 aut
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| 245 |
1 |
0 |
|a CD137 expression and signal function drive pleiotropic γδ T-cell effector functions that inhibit intracellular M. tuberculosis growth
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| 264 |
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1 |
|c 2024
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| 336 |
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|a Text
|b txt
|2 rdacontent
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| 337 |
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|a ƒaComputermedien
|b c
|2 rdamedia
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| 338 |
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|a ƒa Online-Ressource
|b cr
|2 rdacarrier
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| 500 |
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|a Date Completed 16.08.2024
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|a Date Revised 26.09.2024
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|a published: Print-Electronic
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|a Citation Status MEDLINE
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|a Copyright © 2024. Published by Elsevier Inc.
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|a Co-activation signal that induces/sustains pleiotropic effector functions of antigen-specific γδ T cells remains unknown. Here, Mycobacteria tuberculosis (Mtb) tuberculin administration during tuberculosis (TB) skin test resulted in rapid expression of co-activation signal molecules CD137 and CD107a by fast-acting Vγ2Vδ2 T cells in TB-resistant subjects (Resisters), but not patients with active TB. And, anti-CD137 agonistic antibody treatment experiments showed that CD137 signaling enabled Vγ2Vδ2 T cells to produce more effector cytokines and inhibit intracellular Mtb growth in macrophages (Mɸ). Consistently, Mtb antigen (Ag) HMBPP stimulation induced sustainable high-level CD137 expression in fresh and activated Vγ2Vδ2 T cells from uninfected subjects, but not TB patients. CD137+Vγ2Vδ2 T-cell subtype predominantly displayed central memory phenotype and mounted better proliferative responses than CD137-Vγ2Vδ2 T-cells. In response to HMBPP, CD137+Vγ2Vδ2 T-cell subtype rapidly differentiated into greater numbers of pleiotropic effector cells producing anti-Mtb cytokines compared to CD137-Vγ2Vδ2 T subtype, with the non-canonical NF-κB pathway involved. CD137 expression in Vγ2Vδ2 T cells appeared to signal anti-Mtb effector functions leading to intracellular Mtb growth inhibition in Mɸ, and active TB disrupted such CD137-driven anti-Mtb effector functions. CD137+Vγ2Vδ2 T-cells subtype exhibited an epigenetic-driven high-level expression of GM-CSF and de novo production of GM-CSF critical for Vγ2Vδ2 T-cell controlling of Mtb growth in Mϕ. Concurrently, exosomes produced by CD137+Vγ2Vδ2 T cells potently inhibited intracellular mycobacterial growth. Furthermore, adoptive transfer of human CD137+Vγ2Vδ2 T cells to Mtb-infected SCID mice conferred protective immunity against Mtb infection. Thus, our data suggest that CD137 expression/signaling drives pleiotropic γδ T-cell effector functions that inhibit intracellular Mtb growth
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|a Journal Article
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|a Anti-tuberculosis activity
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| 650 |
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4 |
|a CD137
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| 650 |
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4 |
|a GM-CSF
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| 650 |
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4 |
|a Mycobacterium tuberculosis
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| 650 |
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4 |
|a γδ T cells
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| 650 |
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7 |
|a Antigens, Bacterial
|2 NLM
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| 650 |
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7 |
|a Cytokines
|2 NLM
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| 650 |
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7 |
|a Receptors, Antigen, T-Cell, gamma-delta
|2 NLM
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| 650 |
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7 |
|a TNFRSF9 protein, human
|2 NLM
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| 650 |
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7 |
|a Tumor Necrosis Factor Receptor Superfamily, Member 9
|2 NLM
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| 700 |
1 |
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|a Huang, Guixian
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Peng, Ying
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Wang, Juechu
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Cai, Xia
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Yang, Enzhuo
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Zhu, Liying
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Wu, Yuan
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Sha, Wei
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Wang, Feifei
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Shen, Ling
|e verfasserin
|4 aut
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| 700 |
1 |
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|a Shen, Hongbo
|e verfasserin
|4 aut
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| 773 |
0 |
8 |
|i Enthalten in
|t Clinical immunology (Orlando, Fla.)
|d 1999
|g 266(2024) vom: 20. Sept., Seite 110331
|w (DE-627)NLM098196855
|x 1521-7035
|7 nnns
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| 773 |
1 |
8 |
|g volume:266
|g year:2024
|g day:20
|g month:09
|g pages:110331
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| 856 |
4 |
0 |
|u http://dx.doi.org/10.1016/j.clim.2024.110331
|3 Volltext
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|a GBV_USEFLAG_A
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|a SYSFLAG_A
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|a GBV_NLM
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|a GBV_ILN_11
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|a GBV_ILN_24
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|a GBV_ILN_350
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|a AR
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| 952 |
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|d 266
|j 2024
|b 20
|c 09
|h 110331
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