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Impact of TNF receptor superfamily member costimulation on the transcriptome of in vitro CD3/CD28 activated mouse Tregs

ABSTRACT: Impact of TNF receptor superfamily member costimulation on the transcriptome of in vitro CD3/CD28 activated mouse Tregs

PROVIDER: PRJNA609358 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR11209323_1.fastq.gz	Fastqsanger.gz
	SRR11209323_2.fastq.gz	Fastqsanger.gz
	SRR11209324_1.fastq.gz	Fastqsanger.gz
	SRR11209324_2.fastq.gz	Fastqsanger.gz
	SRR11209325_1.fastq.gz	Fastqsanger.gz

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Impact of TNF receptor superfamily member costimulation on the transcriptome of in vitro CD3/CD28 activated mouse Tregs

Project description:Activated Foxp3+ regulatory T cells (Tregs) express several TNF receptor superfamily (TNFRSF) members. Here, we analyzed the transcriptome of purified Tregs that were activated with anti-CD3 and anti-CD28 mAbs, IL-2 and with or without agonists of TNFR2, 4-1BB, DR3 and OX40 for 18h and 36h. Triggering these TNFRSF in Tregs induces similar changes in gene expression patterns, suggesting that they engage common signal transduction pathways. Among them, we identified a major role of canonical NF-κB.

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Interactomics of the RLTPR protein explain its essential role for costimulation via CD28

Project description:The RLTPR cytosolic protein has an essential role in CD28 costimulation but its mode of action and importance in human T cells remain elusive. Here, using mass spectrometry we showed that CD28, RLTPR and the CARMA1 cytosolic adaptor physically associate in mouse T cells. Although RLTPR is thought to function as an actin-uncapping protein, this property was dispensable for CD28 costimulation. Our findings underpin the convergent function of RLTPR in T cells and suggest that its scaffolding role predominates during CD28 costimulation.

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Effect of costimulation on microRNAs levels in human naïve CD4 T cells

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Project description:Immune responses depend on a dynamic balance between the opposing activities of conventional (Tconv) and regulatory (Treg) CD4+ T cells. While receptor-targeted approaches have been developed based on their modulation of Tconv cells, Tconv and Treg cells share many costimulatory receptors. We aim to determine key differential signaling events downstream of costimulation to find opportunities for selective manipulation of Tconv or Treg cells. This data set includes the transcriptomes of expanded human Tconv and Treg cells that were treated with anti-CD3, anti-CD3/CD28 or anti-CD3/TNFR2 agonistic mAbs for 24 hours.

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Project description:The local mechanisms regulating exhaustion of tumor-infiltrating lymphocytes (TILs) and responsiveness to PD-1 blockade remain partly elucidated. In human ovarian cancer we show that tumor-reactive intraepithelial (ie)CD8+ TILs engaged by antigen are polyfunctional and upregulate PD-1, which restrains their effectiveness. PD-1+ TILs exhibit a continuum of TCR-engaged/exhausted states with variable effector fitness related to CD28 costimulation, which they receive in intraepithelial niches involving myeloid antigen-presenting cells (mAPC). Following PD-1 blockade, activation of TILs requires CD28 costimulation mediated in situ by tumor mAPCs, which is locally enhanced by CTLA-4 blockade. CD40 ligand also amplifies TIL responses in situ, especially in tumors in which mAPCs are not activated. Thus, dysfunctional and exhausted TILs, in a state of TCR engagement but without proper CD28 costimulation by mAPCs in situ, are unlikely to fully benefit from PD-1 blockade.

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