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Comparison of different T cell differentiation states by RNA-seq analysis identifies BX-795 induced Th-IL-2 cells

ABSTRACT: We here report RNA-seq data on CD4+ T cells from double transgenic allergy-mice (Neunkirchner A. et al.) expressing a humanized T cell receptor (TCR) specific for the major mugwort pollen allergen Art v 1 peptide 23-36 in combination with a humanized HLA-DR molecule at time-point zero (FACS sorted naive CD4+ T cells from murine spleen) and after 120 h of stimulation of such FACS sorted naive T cells with bone-marrow derived dendritic cells (BMDCs) from these mice plus recombinant Art v 1 (rArt v 1) protein and either DMSO (T effector), BX-795 (Th-IL-2) or a mix of TGF-b, anti-IL-4 and anti-IFN-g (iTreg). T cells cultured for 120 h were FACS sorted before RNA extraction to exclude BMDCs (purity > 90 %). These data is supposed to characterize the expression phenotype of T cells differentiated in the presence of BX-795 (Th-IL-2) and extract specific features by comparing it to control phenotypes (naive, T effector, iTreg).

ORGANISM(S): Mus musculus

PROVIDER: GSE224271 | GEO | 2023/03/17

REPOSITORIES: GEO

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Project description:Some unicellular organisms exhibit collective decision-making through intercellular communication once a quorum of members sense an environmental stress. Whether T cells at different states of differentiation may also synchronize their behavior on a population basis through direct interactions remains unclear. We report that memory CD8+ T cells (TMem) directly interact with naive T cells (TN) during priming, affecting the phenotypic, functional, transcriptional and metabolic differentiation of TN-derived progeny. This previously unrecognized, contact and concentration-dependent interaction between naive (TN) and memory CD8+ T cells (TMem) directly enhanced TN effector differentiation through non-apoptotic Fas signaling resulting in downstream Akt pathway activation. TN primed with TMem exhibited significantly impaired persistence and antitumor activity compared with TN primed alone. Disruption of FasL-Fas signaling in TN cells limited differentiation and enhanced anti-tumor immunity while provision of exogenous FasL in the absence of TMem impaired anti-tumor immunity by augmenting TN differentiation. These findings reveal that the full therapeutic potential of TN-derived cells for adoptive immunotherapy requires physical separation from TMem prior to priming or antagonism of Fas-signaling. FACS-sorted in vitro differentiated TMem samples were without stimulation (0 hours) (n=3), and FACS-sorted in vitro differentiated TMem samples were stimulated using CD3-specific and CD28-specific antibodies and IL-2 for 18 (n=3) and 96 (n=3) hours. FACS-sorted naive Pmel-1 CD8+ T cell samples were without stimulation (0 hours) (n=3), and FACS-sorted TN-derived Pmel-1 CD8+ T cell samples were stimulated using CD3-specific and CD28-specific antibodies and IL-2 for 18 (n=3) and 96 (n=3) hours. FACS-sorted TN-derived Pmel-1 CD8+ T cell samples were stimulated in the presence of TMem using CD3-specific and CD28-specific antibodies and IL-2 for 18 (n=3) and 96 (n=3) hours. FACS-sorted in vitro differentiated TMem samples were stimulated in the presence of TN using CD3-specific and CD28-specific antibodies and IL-2 for 18 (n=3) and 96 (n=3) hours. All samples were done in triplicate as biological repeats.

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Comparison of different T cell differentiation states by RNA-seq analysis identifies BX-795 induced Th-IL-2 cells

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