Impact of gamma chain cytokines on the differentiation of recently antigen-activated CD8 T cells
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE58262 | GEO | 2014/06/06
SECONDARY ACCESSION(S): PRJNA251757
REPOSITORIES: GEO
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Project description:Analysis of how different gamma chain family cytokines influence CD8 T cell differentiation. Naïve CD8 T cells were isolated from the spleens OT-I Thy1.1 TCR Tg mice. Whole splenocytes from wild-type C57BL/6 mice were used as stimulator cells. Purified naïve wild-type OT-I (1×106/well) were stimulated with OVA peptide (SIINFEKL) pulsed (5 µg/ml) and irradiated (2,000 rads) syngeneic splenocytes (6×106/well) in 24-well plates. Forty-eight hours later, activated OT-I T cells were harvested and viable cells were enriched over a Ficoll-paque gradient and washed with cRPMI prior to being reseeded in cRPMI (5×105 cells/ml) and treated with the media supplemented with various γc cytokines (IL-2, IL-4, IL-7, IL-15 and IL-21). Experimental samples were treated with 100 ng/ml of their respective gamma chain cytokine and incubated at 37ºC for 24 hours. RNA was isolated using either the RNeasy Mini kit, or a combination of TRIzol reagent and the Direct-zol RNA miniprep kit, all following manufacturer protocols. Two biological replicates for mRNA analysis were prepped using the RNeasy kit. The third replicate was prepped using the Trizol/Direct-zol approach. The quality and quantity of RNA samples was further analyzed on the Bioanalyzer. Labeled target cDNA was prepared from total RNA samples using the Ambion MessageAmp Premier protocol (3’IVT assay). Each sample target was hybridized to a Mouse 430 2.0 GeneChip array. Image processing and expression analysis were performed using Affymetrix GeneChip Command Console (AGCC) v. 3.1.1 and Affymetrix Expression Console v.1.1 software, respectively. Data from all biological replicates and conditions was imported into the Affymetrix Expression Console and normalized (RMA). RNA processing and microarray hybridization were performed by the Oregon Health & Science University Gene Microarray Shared Resource core facility in Portland, Oregon.
2014-06-06 | E-GEOD-58262 | biostudies-arrayexpress
Project description:Profiling of early in-vivo responses to the 6 common gamma-chain family cytokines, in 14 immunologic cell-types.
2022-01-01 | GSE180020 | GEO
Project description:ImmGen cytokines: Signatures of “common γ-chain” family cytokines
| PRJNA746283 | ENA
Project description:BackgroundSeveral members of the common gamma chain (gc) cytokine family are already approved (IL-2) or actively being developed as vaccine adjuvants and cancer immunotherapies. Studies have indicated that co-administration of gc cytokines may enhance the efficacy of immunotherapies that function via direct activation of co-stimulatory T cell receptors. To define the specific influence of gc cytokines on the co-stimulatory capacity of CD8(+) T cells and identify combinations with synergistic potential, we investigated the direct impact of gc cytokines on the differentiation and transcriptional profile of recently antigen-primed CD8(+) T cells.MethodsNaïve CD8(+) T cells were activated with peptide-pulsed APCs. After 48 hours, CD8(+) T cells were harvested and re-cultured in media supplemented with IL-2, IL-4, IL-7, IL-15 or IL-21. After 24 hours, cells were analyzed by cytokine bead array, flow cytometry, and mRNA micro-array. Gene networks responsible for specific CD8(+) T cell functions were constructed through literature-meta review and publicly available annotation databases. Gene expression data from the experimental groups was imported into this network to visualize the impact of each gc cytokine on the functional polarization of recently-activated CD8(+) T cells.ResultsAmong the gc cytokines, IL-2 induced the greatest increase in the expression of co-stimulatory receptors in recently-activated CD8(+) T cells. IL-2 increased significantly expression of 4-1BB, GITR, ICOS and OX40, at both the transcriptional and protein level. IL-2 also drove the greatest increase in cellular proliferation and the most robust shift towards a pro-survival phenotype, compared with the other gc cytokines. Both IL-4 and IL-21 enhanced expression of cytotoxic effector proteins, but drove distinct phenotypic polarizations, Th2/Tc2 and NK-like, respectively.ConclusionsOverall, these observations suggest that among gc cytokines, IL-2 may be uniquely capable of synergizing with therapeutic strategies that combine immunization with agonists of co-stimulatory T cell receptors. Previous studies have shown that the timing of IL-2 treatment relative to immunization plays a key role in defining the CD8(+) T cell response, and the findings from this study indicate that administration of exogenous IL-2 shortly after the initial antigen-priming event has concluded may augment the receptivity of these cells to subsequent TNFR co-stimulation.
| S-EPMC4236884 | biostudies-literature
Project description:The interweaved signatures of common-gamma-chain cytokines across immunologic lineages
| PRJNA858460 | ENA
Project description:"γc" cytokines are a family whose receptors share a “common gamma chain” signaling moiety, and play central roles in the differentiation, homeostasis and communications of all immunocyte lineages. As a resource to better understand their range and specificity of action, we profiled by RNAseq the immediate-early responses to the main γc cytokines, across all immunocyte lineages. The results show a different response landscape than expected: broader, with a strong Myc-controlled resetting of biosynthetic and metabolic pathways, a major downregulation component, and extensive overlap between cytokines (one cytokine doing in one cell what another does elsewhere). Various mechanisms appear involved: fast transcriptional activation, chromatin remodeling, and mRNA destabilization. Other surprises are uncovered: IL2 effects in mast cells, major shifts between follicular and marginal-zone B cells, paradoxical and cell-specific cross-talk between IFN and γc signaling, or an NK-T like program induced by IL21 in CD8+ T cells.
2022-07-22 | GSE208138 | GEO
Project description:BACKGROUND:CD8+CD28- T suppressor (Ts) cells play critical role in transplant tolerance. Our previous study has generated CD8+CD28- Ts cells in vitro which exert robust allospecific suppressive capacity in vitro. RESULTS:CD8+CD28- Ts cells were expanded by stimulating human CD8+ T cells with allogeneic antigen presenting cells in the presence of the common gamma chain cytokines IL-2, IL-7 and IL-15 in vitro, and were further verified in vitro through day 7 to 11 for their persistency of the allospecific suppressive capacity. When CD8+CD28- Ts cells were adoptively transferred into NOG mice, their capacity to inhibit CD4+ T cell proliferation in allospecific manner remained potent on 11?days after their injection. The mechanisms for expansion of CD8+CD28- Ts cells by the common gamma chain cytokines were investigated. These included promoting CD8+CD28- T cells proliferation, converting CD8+CD28+ T cells to CD8+CD28- T cells and decreasing CD8+CD28- T cell death. Furthermore, the expanded CD8+CD28- Ts cells showed upregulation of the co-inhibitory molecule Tim-3 and down-regulation of the cytotoxic molecule granzyme B. CONCLUSIONS:In summary, these results demonstrated that the in vitro-expanded human CD8+CD28- T cells retained potent allospecific suppressive capacity in vivo and depicted multiple mechanisms for the expansion of Ts cells, which might promote further bench to clinic research.
| S-EPMC7189520 | biostudies-literature
Project description:Junctional adhesion molecule-like protein (JAML) serves as a co-stimulatory molecule in γδ T cells. While it has recently been described as a cancer immunotherapy target in mice, its potential to cause toxicity, specific mode of action with regard to its cellular targets, and whether it can be targeted in humans remain unknown. Here, we show that JAML is induced by T cell receptor engagement, reveal that this induction is linked to cis-regulatory interactions between the CD3D and JAML gene loci. When compared with other immunotherapy targets plagued by low target specificity and end-organ toxicity, we find JAML to be mostly restricted to and highly expressed by tissue-resident memory CD8+ T cells in multiple cancer types. By delineating the key cellular targets and functional consequences of agonistic anti-JAML therapy in a murine melanoma model, we show its specific mode of action and the reason for its synergistic effects with anti-PD-1.
| S-EPMC10366340 | biostudies-literature
Project description:Common ? chain (?C) cytokines, namely IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 are important for the proliferation, differentiation, and survival of lymphocytes that display antitumor activity, thus stimulating considerable interest for the use of cytokines in cancer immunotherapy. In this review, we will focus on the ?C cytokines that demonstrate the greatest potential for immunotherapy, IL-2, IL-7, IL-15, and IL-21. We will briefly cover their biological function, potential applications in cancer therapy, and update on their use in combinatorial immune strategies for eradicating tumors and hematopoietic malignancies.
| S-EPMC4710466 | biostudies-literature