HCSGD entry for CD28
1. General information
| Official gene symbol | CD28 |
|---|---|
| Entrez ID | 940 |
| Gene full name | CD28 molecule |
| Other gene symbols | Tp44 |
| Links to Entrez Gene | Links to Entrez Gene |
2. Neighbors in the network
3. Gene ontology annotation
GO ID | GO term | Evidence | Category |
|---|---|---|---|
| GO:0002020 | Protease binding | IPI | molecular_function |
| GO:0002863 | Positive regulation of inflammatory response to antigenic stimulus | IEA | biological_process |
| GO:0005070 | SH3/SH2 adaptor activity | IDA | molecular_function |
| GO:0005515 | Protein binding | IPI | molecular_function |
| GO:0005829 | Cytosol | TAS | cellular_component |
| GO:0005886 | Plasma membrane | IDA TAS | cellular_component |
| GO:0005887 | Integral component of plasma membrane | TAS | cellular_component |
| GO:0006959 | Humoral immune response | TAS | biological_process |
| GO:0007166 | Cell surface receptor signaling pathway | TAS | biological_process |
| GO:0007173 | Epidermal growth factor receptor signaling pathway | TAS | biological_process |
| GO:0008543 | Fibroblast growth factor receptor signaling pathway | TAS | biological_process |
| GO:0009897 | External side of plasma membrane | IDA | cellular_component |
| GO:0009967 | Positive regulation of signal transduction | IDA | biological_process |
| GO:0015026 | Coreceptor activity | TAS | molecular_function |
| GO:0016032 | Viral process | TAS | biological_process |
| GO:0031295 | T cell costimulation | TAS | biological_process |
| GO:0038095 | Fc-epsilon receptor signaling pathway | TAS | biological_process |
| GO:0042089 | Cytokine biosynthetic process | TAS | biological_process |
| GO:0042102 | Positive regulation of T cell proliferation | IDA ISS TAS | biological_process |
| GO:0042802 | Identical protein binding | NAS | molecular_function |
| GO:0045060 | Negative thymic T cell selection | IEA | biological_process |
| GO:0045066 | Regulatory T cell differentiation | IDA | biological_process |
| GO:0045070 | Positive regulation of viral genome replication | NAS | biological_process |
| GO:0045086 | Positive regulation of interleukin-2 biosynthetic process | IDA ISS | biological_process |
| GO:0045087 | Innate immune response | TAS | biological_process |
| GO:0045727 | Positive regulation of translation | NAS | biological_process |
| GO:0045840 | Positive regulation of mitosis | IDA ISS | biological_process |
| GO:0045944 | Positive regulation of transcription from RNA polymerase II promoter | IEA | biological_process |
| GO:0046641 | Positive regulation of alpha-beta T cell proliferation | IEA | biological_process |
| GO:0048011 | Neurotrophin TRK receptor signaling pathway | TAS | biological_process |
| GO:0048015 | Phosphatidylinositol-mediated signaling | TAS | biological_process |
| GO:0048304 | Positive regulation of isotype switching to IgG isotypes | IEA | biological_process |
| GO:0050690 | Regulation of defense response to virus by virus | TAS | biological_process |
| GO:0097190 | Apoptotic signaling pathway | IEA | biological_process |
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4. Expression levels in datasets
- Meta-analysis result
| p-value up | p-value down | FDR up | FDR down |
|---|---|---|---|
| 0.2738406747 | 0.9645290377 | 0.9702713190 | 1.0000000000 |
- Individual experiment result
( "-" represent NA in the specific microarray platform )
( "-" represent NA in the specific microarray platform )
| Data source | Up or down | Log fold change |
|---|---|---|
| GSE11954 | Up | 0.1193833940 |
| GSE13712_SHEAR | Up | 0.1760908132 |
| GSE13712_STATIC | Down | -0.0401989527 |
| GSE19018 | Up | 0.0698139789 |
| GSE19899_A1 | Up | 0.0784325384 |
| GSE19899_A2 | Up | 0.0660560048 |
| PubMed_21979375_A1 | Up | 0.1398348351 |
| PubMed_21979375_A2 | Up | 0.1745987750 |
| GSE35957 | Up | 0.0493963826 |
| GSE36640 | Up | 0.1087259529 |
| GSE54402 | Down | -0.0075790724 |
| GSE9593 | Up | 0.0322691842 |
| GSE43922 | Up | 0.0157653252 |
| GSE24585 | Up | 0.1820176249 |
| GSE37065 | Up | 0.0281039731 |
| GSE28863_A1 | Up | 0.0160928308 |
| GSE28863_A2 | Up | 0.4738279108 |
| GSE28863_A3 | Up | 0.0858688546 |
| GSE28863_A4 | Up | 0.1453894046 |
| GSE48662 | Up | 0.0699903169 |
5. Regulation relationships with compounds/drugs/microRNAs
- Compounds
Not regulated by compounds
- Drugs
Not regulated by drugs
- MicroRNAs
- mirTarBase
MiRNA_name | mirBase ID | miRTarBase ID | Experiment | Support type | References (Pubmed ID) |
|---|---|---|---|---|---|
| hsa-miR-26b-5p | MIMAT0000083 | MIRT029645 | Microarray | Functional MTI (Weak) | 19088304 |
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- mirRecord
No target information from mirRecord
6. Text-mining results about the gene
Gene occurances in abstracts of cellular senescence-associated articles: 39 abstracts the gene occurs.
PubMed ID of the article | Sentenece the gene occurs |
|---|---|
| 28082969 | Aging of the immune system, also termed as immunosenescence, involves many changes in human T cell immunity that is characterized by a loss in naive T cell population and an increase in highly differentiated CD28- memory T cell subset |
| 28066427 | They also demonstrated increased cytotoxicity toward lung epithelial cells and importantly were resistant to immunosuppression by corticosteroids compared with their CD28+ counterparts |
| 26950734 | Loss of CD28 on Peripheral T Cells Decreases the Risk for Early Acute Rejection after Kidney Transplantation |
| 26711627 | METHODS: Changes in CD8+ T-cell subsets, based on the expression of CD28 and CD57, were analysed in patients with various forms of cancer affecting the lungs, undergoing chemotherapy and in a control group over six months, using multi-colour flow cytometry |
| 26451160 | CONCLUSIONS: This study is the first to employ circular RNA profiling to investigate circular RNA-micro RNA interactions in ageing human CD8(+)T cell populations and the accompanying loss of CD28 expression |
| 26277688 | Aging-associated subpopulations of human CD8+ T-lymphocytes identified by their CD28 and CD57 phenotypes |
| 26277688 | METHODS: We identified, by flow cytometry, subpopulations of CD8+ T-cells based on CD57 and CD28 expression, and tested them for some markers of cellular senescence, apoptosis, differentiation and homing |
| 25604328 | Immunosenescence was investigated by analysing CD57(+) CD28(-) levels, immune activation by analysing CD38(+) HLA-DR(+) levels, inflammation by analysing interleukin (IL)-6 levels, and microbial translocation by analysing lipopolysaccharide (LPS) and soluble CD14 (sCD14) levels |
| 25001861 | The classical markers of alpha/beta T cell aging, including CD28, CD27, and CD57, did not prove significant for gamma/delta T cells |
| 24586733 | Given that CD28 and IL-2 play important roles in Treg function, the relationships between premature CD4(+) T cell aging and lymphopenia as well as Treg defects in autoimmune-prone NOD mice are proposed |
| 24231352 | Cultured CD8+ blood T lymphocytes underwent replicative senescence that was associated with loss of CD28 and Delta133p53 protein |
| 24231352 | In poorly proliferative, Delta133p53-low CD8+CD28- cells, reconstituted expression of either Delta133p53 or CD28 upregulated endogenous expression of each other, which restored cell proliferation, extended replicative lifespan and rescued senescence phenotypes |
| 23686519 | OBJECTIVE: CD8+ T cells lacking CD28 were originally reported to be a characteristic feature of juvenile idiopathic arthritis (JIA), but the relevance of these unusual cells to this disease remains to be elucidated |
| 25392765 | The CD8 T cell phenotype was defined by the surface expression of CD28 and CD95 |
| 23435301 | RESULTS: There was increased frequency of CD4+ and CD8+ T cells with an immunosenescence phenotype (CD57+ and CD28-) in cases vs |
| 23435301 | Cases had lower proportions of naive T cells (CD27+ CD28+ CD45RA+) in CD4+ (23 |
| 22613541 | The frequency of CD28 and CD95 demonstrated a "curved" rather than linear tendency by age |
| 22560928 | Prominent examples are the expression of negative regulatory receptors of the CD28 and the TNF receptor superfamilies as well the expression of various cytoplasmic and nuclear dual-specific phosphatases |
| 22448010 | T-cell senescence, characterized by expansion of cells lacking the costimulatory molecule CD28, has been hypothesized to mediate these risks |
| 22448010 | For CD8(+) cells, younger age and HCV infection were associated with a lower %CD28(-) |
| 22448010 | ART reduced %CD28(-) levels at week 96 among virally suppressed individuals |
| 22448010 | Compared to HIV-uninfected individuals, HIV-infected individuals maintained significantly higher %CD28(-) |
| 22102004 | CD28-, CD57+ and KLRG1+ are cell surface markers that have been used to describe senescent T-lymphocytes in humans |
| 22102004 | Using five-colour flow cytometry, we analyzed peripheral blood T-lymphocytes for their expression of CD28, CD57 and KLRG1 in 11 young (Y) and 11 old (O) apparently healthy human subjects |
| 22102004 | The proportions of CD28- and CD57+ cells were significantly higher among the T-cell populations of O compared to Y subjects; the proportion of KLRG1+ cells was significantly higher only among CD8+ cells |
| 22102004 | Populations that were more frequent in the elderly participants were characterised as CD28+ CD57+, CD28- CD57+ or CD28- CD57- |
| 21562872 | UNLABELLED: Presently the relationship between CD28, biological marker of senescence, and ovariectomy is not well understood |
| 21562872 | We show that ovariectomy leads to CD28 loss on T cells and estrogen (E2) repletion and medicarpin (Med) inhibits this effect |
| 21562872 | We aim to determine the effect of Ovx on CD28 expression on T cells and effects of E2 and medicarpin (a pterocarpan phytoalexin) with proven osteoprotective effect on altered T cell responses |
| 21562872 | Med/E2 reduced BM and spleen CD4(+) T cell proliferation and prevented CD28 loss on CD4(+) T cells |
| 21562872 | Further, Med abrogated TNF-alpha-induced loss of CD28 expression in the BM T cells |
| 21562872 | CONCLUSIONS: To our knowledge this is the first report to determine the mechanism of CD28 loss on T cells as a result of ovariectomy |
| 21562872 | We propose that one of the mechanisms by which Med/E2 alleviates Ovx-induced bone loss is by delaying T cell senescence and enhancing CD28 expression |
| 20933612 | We will first detail T cell signaling through the T cell receptor (TCR), CD28 and IL-2 receptor (IL-2R) and then discuss the observed age-related alterations to these signaling pathways |
| 20137575 | Altered CD28 and CD95 mRNA expression in peripheral blood mononuclear cells from elderly patients with primary non-small cell lung cancer |
| 20137575 | BACKGROUND: The expression of the co-stimulatory molecule CD28 and death receptor CD95 on T cells, which change with age, are considered as important immunological parameters of immunosenescence |
| 20137575 | It is well established that CD28 and CD95 are associated with tumorgenesis and tumor progression, but the relationship between the age-related changes of these two immunological markers and cancer in the elderly is largely unknown |
| 20137575 | METHODS: The levels of CD28 and CD95 mRNA in peripheral blood mononuclear cells (PBMCs) from sixty-three elderly patients (aged > or = 60 years) with primary non-small cell lung cancer (NSCLC) were analyzed by real-time fluorescence-based quantitative polymerase chain reaction (FQ-PCR) |
| 20137575 | RESULTS: CD28 mRNA levels were significantly lower and CD95 mRNA levels were significantly higher in elderly patients with NSCLC than in the other groups |
| 20137575 | By Logistic regression analysis an increased risk of NSCLC was markedly associated with aging, down-regulation of CD28 mRNA and up-regulation of CD95 mRNA, and CD28 mRNA had an obvious negative correlation with the CD95 mRNA |
| 20137575 | In addition, the mRNA levels of CD28 and CD95 in the peripheral blood of the elderly patients was closely associated with the tumor node metastasis (TNM) stages, grade of cell differentiation and lymph node metastasis status, but not related to pathological types |
| 20137575 | CONCLUSIONS: The results suggest a close relationship between T cell senescence and NSCLC tumour progress in the elderly, and that up-regulation of CD28 mRNA or down-regulation of CD95 mRNA in peripheral blood T cells may play an important role in inhibiting oncogenesis and development of primary NSCLC in the elderly |
| 19602548 | As early as 2 months after HSCT, CD8(+) T cells from patients were predominantly CD28(-) CD57(+) and had relatively short telomeres, consistent with cellular senescence |
| 19220836 | Populations of CD4(+) T cells lacking surface co-stimulatory CD28 were enlarged significantly in evaluated patients when compared with controls |
| 17379755 | Blood lymphocytes isolated before, immediately after, and 1 h after exercise were assessed for cell surface expression of KLRG1, CD57, CD28, CD45RA, CD45RO, CD62L, and lymphocyte subset markers (CD3, CD4, CD8, CD56) by flow cytometry |
| 17202338 | To support this hypothesis, we show here that the reduction of Klotho expression and activity in both elderly and patients' lymphocytes occurs in concert with the down-regulation of T cell costimulatory molecule CD28, the latter known to be dependent on increased levels of TNF-alpha |
| 17195207 | OBJECTIVE: T cells deficient in CD28 expression have been implicated in the pathogenesis of rheumatoid arthritis (RA) |
| 17195207 | RESULTS: Chronic stimulation of CD28(+) T cells in vitro yielded progenies that lacked CD28 but that gained CD56 |
| 17195207 | CONCLUSION: Chronic activation of T cells induces counterregulation of CD28 and CD56 expression |
| 17195207 | The loss of CD28 is accompanied by the gain of CD56 that confers TCR-independent and TCR-dependent activation pathways |
| 17117905 | In the present study, we will evaluate in CD8 lymphocytes from patients undergoing acute renal rejection characteristics of replicative senescence such as: a) low expression of CD28 molecule; b) telomere shortening and c) increase production of proinflammatory cytokines |
| 16461801 | CD4 T cells in the senescence program were identified by the loss of CD28 |
| 15882354 | In this study, we present an analysis of the global gene expression profiles of CD28(+) and CD28(null) memory phenotype CD8(+) T cells |
| 15882354 | A wide range of functions, including co-stimulation, effector activity, signaling, and transcription, were possessed by these differentially expressed genes, reflecting significant functional changes of CD28(null) memory phenotype CD8(+) T cells from their CD28(+) counterparts |
| 15882354 | Our analysis provides the gene expression portraits of CD28(null) memory phenotype CD8(+) T cells and alteration from their CD28(+) counterparts and suggests potential mechanisms of T-cell aging |
| 15882352 | CD28 extinction in human T cells: altered functions and the program of T-cell senescence |
| 15882352 | The loss of CD28 expression on T cells is the most consistent biological indicator of aging in the human immune system, and the frequency of CD28(null) T cells is a key predictor of immune incompetence in the elderly |
| 15882352 | Unlike the situation in CD28 gene knockout mice that have anergic CD28(0/0) T cells, human CD28(null) T cells are functionally active, long-lived, oligoclonal lymphocytes that lack or have limited proliferative capacity |
| 15882352 | Results of replicative senescence studies show that CD28(null) T cells are derived from CD28(+) precursors that have undergone repeated stimulation, indicating that CD28 silencing underlies the program of T-cell aging |
| 15882352 | Dissection of the machinery regulating CD28 expression is paving the way in elucidating the molecular events leading to immune senescence as well as providing clues into the functional rejuvenation of senescent T cells |
| 15102354 | Long-lived clonal T cells deficient in CD28 expression are commonly found in patients with inflammatory syndromes and persistent infections |
| 15102354 | Considering that CD28 loss is the most consistent immunological marker of aging, we propose that, in pathological states, CD28(null) T cells represent prematurely senescent cells resulting from persistent immune activation |
| 15102354 | Indeed, studies on the molecular basis for the loss of CD28 are already providing information on methods to functionally rescue senescent T cells |
| 12915205 | T-cell immunosenescence is associated with profound changes in T-cell functional profile and leads to accumulation of CD4+ T cells that have lost CD28 but have gained killer immunoglobulin-like receptors and cytolytic capability and produce large amounts of interferon-gamma |
| 12869504 | Our results show that sharp differences exist between the CD8 and CD4 T-cell subsets in (1) cell-cycle programs (as assessed by both in vitro proliferation and in vivo turnover measurement); (2) CD28 regulation on cell-cycle entry; and (3) accumulation of immediate effector cells among the CD28- cells, believed to be close to or at replicative senescence |
| 12869504 | These results further suggest poor reliability of CD28 as a marker for senescence |
| 11985666 | We also analysed the expression of naive cell-associated markers, CD28, CD62L and CD45RA/CD62L in T lymphocytes of 47 cynomolgus monkeys |
| 11985666 | An age-related increase in the CD28- subset was observed in CD8+ T lymphocytes in monkeys less than 11 years old and in CD4+ T lymphocytes in monkeys over 23 years old, respectively |
| 11554612 | Fresh NAMNC, non-stimulated or activated in vitro with PHA or with a mixture of monoclonal antibodies against CD3 and against CD28 membrane antigens (in order to obtain prevalent T cell responses), were exposed to Saquinavir before or at the time of mitogenic stimulation |
| 10352273 | Modulation of CD28 expression: distinct regulatory pathways during activation and replicative senescence |
| 10352273 | The costimulatory molecule CD28 has a restricted tissue distribution and is expressed on T cells and some plasmacytoma cells |
| 10352273 | Although CD28 is constitutively expressed, its expression is transiently down-regulated following T cell activation and declines progressively with in vitro senescence |
| 10352273 | In vivo, CD8+ T cells and, less frequently, CD4+ T cells may completely lose CD28 surface expression during chronic infections and with aging |
| 10352273 | This correlates with changes of nuclear protein-binding activities to two motifs, site alpha and beta, within the CD28 minimal promoter |
| 10352273 | CD4+ and CD8+ T cells differ in their beta-binding profiles, which may explain the more pronounced down-regulation of CD28 in senescent CD8+ T cells |
| 10092696 | In contrast, CD28 tended to be underexpressed in the BAL T cells |
| 9691202 | CD28 expression correlates inversely with cell population doublings |
| 9691202 | When cultured continuously, these CD4+ human T lymphocytes gradually lose expression of CD28 |
| 9615924 | CD28 expression in T cell aging and human longevity |
| 9615924 | Cohorts of 97 centenarians, 40 subjects aged 70-90 (ELD group), and 40 young adults (under age 40) were phenotyped for T cell surface expression of CD28, CD4, and CD8 antigens |
| 9615924 | The significant decline in T cells expressing CD28 (p < 10(-4) for comparisons between adults and either ELD or centenarians) affects preferentially the CD8+ subset of T cells |
| 9615924 | CD28 expression is modulated in T cell cultures in a growth-related fashion and this modulation is dampened in cultures from centenarians |
| 9615924 | We propose that the decrease in CD28 expression reflects a compensatory adaptation of the immune system during aging in the face of chronic stimulation |
| 9435913 | We have compared the peripheral blood T lymphocytes of centenarians and younger controls for the cell surface expression of CD28, a costimulatory molecule that is required for optimal activation and proliferation following engagement of the T cell receptor |
| 9435913 | Concommitantly, experiments using an in vitro T cell culture system showed a progressive loss of CD28 expression with culture "age |
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