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Inherited CD28 deficiency in otherwise healthy patients with disseminated warts and giant horns

ABSTRACT: This study presents the analysis of a patient with the HPV-2-driven Ã¢Â€Âœtree manÃ¢Â€Â phenotype, and two of his distant relatives with unusually severe HPV4-driven warts. All three patients are homozygous for a private CD28 variant. The data available here are 10X Genomics 3' scRNA-seq data of the three patients.

PROVIDER: EGAS00001004837 | EGA |

REPOSITORIES: EGA

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Human CD28 is essential for T-cell immunity to skin-tropic a- and g-papillomaviruses

Project description:In humans, α-papillomavirus HPV-2 and γ-papillomavirus HPV-4 typically cause common warts. In rare patients, HPV-2 may cause striking “tree man” manifestations. We describe here a patient with the HPV-2-driven “tree man” phenotype, and two of his distant relatives with unusually severe HPV4-driven warts. Genetic, transcriptional, and histological analyses of the “tree man” lesions showed that they formed a multifocal benign epithelial tumor driven by a specific HPV-2 strain. Surprisingly, all three patients are homozygous for a mutation of an essential splice site in the CD28 gene, which encodes an activating surface receptor on T cells. They have no detectable CD28 on their T cells, which, with the exception of a small contingent of revertant memory CD4+ T cells, do not respond to CD28 stimulation. Their T cells express normal levels of other costimulatory molecules and CTLA-4, and respond to CD2 stimulation. T- and B-cell development, and responses to antigens are otherwise normal in these individuals. Finally, CD28-deficient mice are vulnerable to cutaneous infections with the μ-papillomavirus MmuPV1. This experiment of Nature shows that the control of HPV-2 and HPV-4 in human keratinocytes is dependent on the T-cell CD28 co-activation pathway, which seems to be otherwise largely redundant in host defense.

2021-07-31 | GSE139299 | GEO

Profiling of Naïve (CD45RA+CD28+), EM (CD45RA-CD28-) and TEMRA (CD45RA+CD28-) CD8+ T cells

Project description:Profiling of Naïve (CD45RA+CD28+), EM (CD45RA-CD28-) and TEMRA (CD45RA+CD28-) CD8+ T cells

| PRJNA530997 | ENA

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.

2016-09-27 | PXD003870 | Pride

Profiling of Naïve (CD45RA+CD28+), EM (CD45RA-CD28-) and TEMRA (CD45RA+CD28-) CD8+ T cells from kidney transplanted patients

Project description:Profiling of Naïve (CD45RA+CD28+), EM (CD45RA-CD28-) and TEMRA (CD45RA+CD28-) CD8+ T cells from kidney transplanted patients

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Differentiated expression profiling between CD8+CD28+ T cell subset and CD8+CD28- T cell subset using long non coding RNA microarray in five healthy Chinese nonagenarians

Project description:To obtain the differentiated profiling of long noncoding RNA expression between CD8+CD28+ T cell subset and CD8+CD28- T cell subset, we have detecte lncRNA profiling between within-individual T cell subsets to identify differentiated lncRNA profiling in five apperant healthy Chinese nenogenarians who were cytomegalovirus-seropositive carriers. Human peripheral blood monocytes from these apperantly healthy CMV-seropositive nonagenarians was gathered. CD8+CD28+ T cells and CD8+CD28- T cells were further isolated using flow cytometry. Differentiated lncRNA profiling was compared between CD8+CD28+ T cells and CD8+CD28- T cells using lncRNA microarry detection within-individually. 586 lncRNAs were found significantly upregulated while 1113 lncRNAs were found significantly downregulated comparing CD8+CD28+ T cells with CD8+CD28- T cells in these Chinese nonagenarians with CMV seropositivity. Expression of ENST00000446590,NR_121652,NR_045006,ENST00000428936,NR_110375 from this differentiated profiling which were identified as previously domumented ageing-related lncRNAs were quantified in the same RNA samples by real-time PCR, confirming lncRNAs take critical role in regulating T cell immunosenesence in healthy nonagenarian Chinese CMV carriers. Diffentiated lncRNA profiling was in-pair compared between total RNAs isolated from CD8+CD28+ T cells and CD8+CD28- T cells within-individually in Chinese nonagenarian CMV carriers.

2016-10-15 | GSE88767 | GEO

Human CD28+/- tumor infiltrating lymphocytes gene expression

Project description:This analysis reveals the different gene expression profiles between human melanoma tumor infiltrating lymphocytes subsets CD8+CD28+ and CD8+CD28-. Adoptive cell therapy (ACT) is an effective approach that removes tumor-infiltrating lymphocytes (TILs) from this suppressive tumor microenvironment and expands and activates CD8+ and CD4+ T cells in vitro, differentiating them into potent anti-tumor effector cells that can be re-introduced back into patients. One of the key problems that may limit tumor regression and long-term durable clinical responses in ACT is the persistence of TILs following infusion. Our study has indicated that ex vivo expanded TILs to be hypo-responsive to peptide re-stimulation, manifested in slow entry into cell cycle and increased apoptosis. Phenotypic and functional analysis using a number of different T-cell differentiation markers found that CD28 was markedly down-modulated in post-REP cells, while CD27 and CD57 levels showed no statistically-relevant changes in expression. Here on a global gene expression level, microarray gene chip analysis of sorted CD8+CD28+ and CD8+CD28- post-REP TILs revealed a number of key differences in their gene expression profiles; notably, an increase in KIR family member expression, loss of p53-binding proteins, and lower CD127/IL-7Ra gene expression found in the CD28- population. On top of advancing T cell phenotype, reactivation and memory, this set of data may also provide insight for ACT clinical protocol optimization to improve TIL response in vivo.

2009-06-10 | GSE16517 | GEO

CD28-CBCA driven PKM splicing licenses CD8 T cell glycolysis and effector function

Project description:CD28-CBCA driven PKM splicing licenses CD8 T cell glycolysis and effector function

| PRJNA714096 | ENA

Transcriptional profile of bone marrow-derived macrophages from Cd28 KO mice

Project description:Analysis of the transcriptome of bone marrow-derived macrophages from Cd28 KO mice. Methods: C57BL/6J (WT) and Cd28 KO (B6.129S2-Cd28tm1Mak/J) mice were used. Bone marrow-derived macrophages were obtained by flushing the femurs of 6- to 10-wk-old C57BL/6, and Cd28 KO mice, and culturing cells during 7 days in DMEM supplemented with 10% FCS and 50 mM 2-ME, containing human M-CSF (25 ng/ml), with cytokine addition every 2 days.

2022-12-01 | GSE157837 | GEO

CD28-CBCA driven PKM splicing licenses CD8 T cell glycolysis and effector function

Project description:T cells stimulated in the absence of CD28 costimulation are functionally anergic, characterized by reduced glucose metabolism and ability to produce effector cytokines. Surprisingly, previous studies have shown relatively few CD28-specific changes in gene transcription upon costimulation. Using mice expressing mutations in the CD28 cytoplasmic tail, we show a major effect of CD28 costimulation is alternative splicing of numerous genes including the glycolytic enzyme pyruvate kinase (Pkm), which is preferentially spliced from Pkm1 to Pkm2 upon stimulation. PKM2 is dispensable for T cell activation, but necessary for CD8+ T cells to utilize aerobic glycolysis, produce effector cytokines, and provide anti-tumor immunity. Mechanistically, CD28 regulates expression of the Cap-Binding Complex adaptor protein ARS2, which binds Pkm splicing factors and facilitates their interaction with the elongating transcript. Data suggest a major function of CD28 costimulation is control of RNA biogenesis in support of T cell transcriptome remodeling and acquisition of effector function.

2023-09-01 | GSE168824 | GEO

CD3/CD28 signaling, Jurkat E6.1, time course 27 mins

Project description:Fe-IMAC phosphoproteomics using TMT 11plex for quant, of Jurkat T cells stimulated with CD3 and CD28 agonist antibodies for 0, 3, 9, or 27 minutes.

| MSV000092965 | MassIVE

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