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Adoptively transferred in vitro-generated MDSCs improve T cell function and antigen-specific immunity after blunt chest trauma-induced lung injury

ABSTRACT: Adoptively transferred in vitro-generated MDSCs improve T cell function and antigen-specific immunity after blunt chest trauma-induced lung injury

PROVIDER: PRJNA777881 | ENA |

REPOSITORIES: ENA

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Adoptively transferred in vitro-generated MDSCs improve T cell function and antigen-specific immunity after blunt chest trauma-induced lung injury

Project description:Does the adoptive transfer of MDSCs modulate lymphocyte (T cell) functions? Microarray expression analysis of T cells from MDSC-treated mice after Blunt chest trauma (TxT)

2022-06-16 | GSE188171 | GEO

Immunostimulatory functions of adoptively transferred MDSCs in experimental blunt chest trauma.

Project description:Myeloid-derived suppressor cells (MDSCs) expand during inflammation and exhibit immunomodulatory functions on innate and adaptive immunity. However, their impact on trauma-induced immune responses, characterized by an early pro-inflammatory phase and dysregulated adaptive immunity involving lymphocyte apoptosis, exhaustion and unresponsiveness is less clear. Therefore, we adoptively transferred in vitro-generated MDSCs shortly before experimental blunt chest trauma (TxT). MDSCs preferentially homed into spleen and liver, but were undetectable in the injured lung, although pro-inflammatory mediators transiently increased in the bronchoalveolar lavage (BAL). Surprisingly, MDSC treatment strongly increased splenocyte numbers, however, without altering the percentage of splenic leukocyte populations. T cells of MDSC-treated TxT mice exhibited an activated phenotype characterized by expression of activation markers and elevated proliferative capacity in vitro, which was not accompanied by up-regulated exhaustion markers or unresponsiveness towards in vitro activation. Most importantly, also T cell expansion after staphylococcal enterotoxin B (SEB) stimulation in vivo was unchanged between MDSC-treated or untreated mice. After MDSC transfer, T cells preferentially exhibited a Th1 phenotype, a prerequisite to circumvent post-traumatic infectious complications. Our findings reveal a totally unexpected immunostimulatory role of adoptively transferred MDSCs in TxT and might offer options to interfere with post-traumatic malfunction of the adaptive immune response.

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Expression data for C. elegans blunt force trauma

Project description:C. elegans exhibit an age-dependent mechanical stress response to blunt force injury. Stress responses are often defined in part by an elicited cellular transcriptional response. We find in C. elegans that mechanical stress by blunt trauma induces a distinct and age-dependent transcriptional program.

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Combination therapy with oncolytic virus and adoptively transferred T cells or mRNA vaccine amplifies antitumor effects [scRNA-Seq]

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2024-03-15 | GSE235290 | GEO

Combination therapy with oncolytic virus and adoptively transferred T cells or mRNA vaccine amplifies antitumor effects [RNA-Seq]

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TLR9-activated B cells imprint adoptively transferred CD8+ T cells with potent tumor immunity and persistence

Project description:Here we report a new way to reverse the tolerant state of adoptively transferred CD8+ T cells against melanoma through ex vivo expansion with the TLR9 agonist CpG. CpG-generated T cells elicited potent immunity without co-administration of high dose IL-2 or vaccination, which are adjuvants classically required to effectively treat solid tumors. CpG-expanded T cells exhibited an IL-2RhighICOShighCD39low phenotype ex vivo and engrafted robustly in vivo. In culture, B cells were the only cell type essential for imprinting T cells with this phenotype and potent tumor immunity. CpG agonists targeting B cells, but not dendritic cells, generated CD8+ T cell products with remarkable antitumor properties. Purified B cells were sufficient to mediate the CpG-associated changes in T cells. These findings reveal a vital role for B cells in the generation of effective antitumor T cells and have immediate implications for profoundly improving immunotherapy for patients.

2022-02-22 | PXD022909 | Pride

Tumor-infiltrating, adoptively transferred BATF-overexpressing CD8 T cells analyzed via bulk RNA-seq

Project description:Tumor-infiltrating, adoptively transferred BATF-overexpressing CD8 T cells analyzed via bulk RNA-seq

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