Granzyme B is an essential mediator in CD8+ T cell killing of<i>Theileria parva</i>-infected cells

Yang, Jie; Pemberton, Alan D.; Morrison, W. Ivan; Connelley, Timothy

doi:10.1101/325662

Cited by 4 publications

(3 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These cells still secreted IFN-g, granzyme b, TNF-a, and perforin, but lost the ability to secrete MIP1a and MIP1b (Figure 3F). This CAd-MSC associated shift in CD8 CAR-T cell phenotype is consistent with induction of greater cytolytic activity 26,27 although the consequences of reduced MIP1a/b secreted from CAR-T cells are less clear.…”

Section: Cad12_pd-l1 Mscs Enhance Effector Function Of Cd4 + Her2 Car...mentioning

confidence: 65%

Mesenchymal stromal cell delivery of oncolytic immunotherapy improves CAR-T cell antitumor activity

et al. 2021

View full text Add to dashboard Cite

Section: Cad12_pd-l1 Mscs Enhance Effector Function Of Cd4 + Her2 Car...mentioning

confidence: 65%

Mesenchymal stromal cell delivery of oncolytic immunotherapy improves CAR-T cell antitumor activity

et al. 2021

View full text Add to dashboard Cite

“…The last but the most potent pFMK molecule in our assay is Z-IETD(OMe)-FMK, with a IC50 of 1.663 μM. It is a specific caspase-8 inhibitor that disrupts the extrinsic caspase pathway [32], and only partially inhibits the cleavage of caspase-3 and PARP. At non-toxic doses, Z-IETD(OMe)-FMK was found to be immunosuppressive.…”

Section: Deep Learning Based Screeningmentioning

confidence: 99%

A novel framework integrating AI model and enzymological experiments promotes identification of SARS-CoV-2 3CL protease inhibitors and activity-based probe

Wang

et al. 2021

Briefings in Bioinformatics

View full text Add to dashboard Cite

The identification of protein–ligand interaction plays a key role in biochemical research and drug discovery. Although deep learning has recently shown great promise in discovering new drugs, there remains a gap between deep learning-based and experimental approaches. Here, we propose a novel framework, named AIMEE, integrating AI model and enzymological experiments, to identify inhibitors against 3CL protease of SARS-CoV-2 (Severe acute respiratory syndrome coronavirus 2), which has taken a significant toll on people across the globe. From a bioactive chemical library, we have conducted two rounds of experiments and identified six novel inhibitors with a hit rate of 29.41%, and four of them showed an IC50 value <3 μM. Moreover, we explored the interpretability of the central model in AIMEE, mapping the deep learning extracted features to the domain knowledge of chemical properties. Based on this knowledge, a commercially available compound was selected and was proven to be an activity-based probe of 3CLpro. This work highlights the great potential of combining deep learning models and biochemical experiments for intelligent iteration and for expanding the boundaries of drug discovery. The code and data are available at https://github.com/SIAT-code/AIMEE.

show abstract

“…Upon reinfection, memory CD8 + T cells proliferate more rapidly than naïve CD8 + T cells [6][7][8][9], resulting in more robust secondary responses to counter invading pathogens upon reinfection. Similar to activated naïve CD8 + T cells, activated memory CD8 + T cells accomplish viral clearance through granzyme B-driven elimination of target cells [10,11] and activation of other immune cells by the release of proinflammatory cytokines, including IFN-γ, TNF-α, and IL-2 [8,12]. These effector properties are considered to be cardinal functions of reactivated memory T cells to mediate protection against reinfection with pathogens.…”

Section: Introductionmentioning

confidence: 99%

Memory CD8⁺ T cells upregulate glycolysis and effector functions under limiting oxygen conditions

et al. 2022

View full text Add to dashboard Cite

Memory CD8 + T cells are indispensable for maintaining long-term immunity against intracellular pathogens and tumors. Despite their presence at oxygen-deprived infected tissue sites or in tumors, the impact of local oxygen pressure on memory CD8 + T cells remains largely unclear. We sought to elucidate how oxygen pressure impacts memory CD8 + T cells arising after infection with Listeria monocytogenes-OVA. Our data revealed that reduced oxygen pressure during in vitro culture switched CD8 + T cell metabolism from oxidative phosphorylation to a glycolytic phenotype. Quantitative proteomic analysis showed that limiting oxygen conditions increased the expression of glucose transporters and components of the glycolytic pathway, while decreasing TCA cycle and mitochondrial respiratory chain proteins. The altered CD8 + T cell metabolism did not affect the expansion potential, but enhanced the granzyme B and IFN-γ production capacity. In vivo, memory CD8 + T cells cultured under low oxygen pressure provided protection against bacterial rechallenge. Taken together, our study indicates that strategies of cellular immune therapy may benefit from reducing oxygen during culture to develop memory CD8 + T cells with superior effector functions.

show abstract

Granzyme B is an essential mediator in CD8+ T cell killing ofTheileria parva-infected cells

Cited by 4 publications

References 51 publications

Mesenchymal stromal cell delivery of oncolytic immunotherapy improves CAR-T cell antitumor activity

Mesenchymal stromal cell delivery of oncolytic immunotherapy improves CAR-T cell antitumor activity

A novel framework integrating AI model and enzymological experiments promotes identification of SARS-CoV-2 3CL protease inhibitors and activity-based probe

Memory CD8⁺ T cells upregulate glycolysis and effector functions under limiting oxygen conditions

Contact Info

Product

Resources

About

Granzyme B is an essential mediator in CD8+ T cell killing ofTheileria parva-infected cells

Cited by 4 publications

References 51 publications

Mesenchymal stromal cell delivery of oncolytic immunotherapy improves CAR-T cell antitumor activity

Mesenchymal stromal cell delivery of oncolytic immunotherapy improves CAR-T cell antitumor activity

A novel framework integrating AI model and enzymological experiments promotes identification of SARS-CoV-2 3CL protease inhibitors and activity-based probe

Memory CD8+ T cells upregulate glycolysis and effector functions under limiting oxygen conditions

Contact Info

Product

Resources

About

Memory CD8⁺ T cells upregulate glycolysis and effector functions under limiting oxygen conditions