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High levels of costimulatory receptors OX40 and 4-1BB characterize CD4+CD28null T cells in patients with acute coronary syndrome.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Dumitriu, Ingrid Elena Baruah, Paramita Finlayson, Caroline J. Loftus, Ian Magnus. Antunes, Ricardo Manuel Fernandes Lim, Pitt O. Bunce, Nicholas H. Kaski, Juan Carlos |
| Copyright Year | 2012 |
| Abstract | RATIONALE Patients with acute coronary syndrome (ACS) predisposed to recurrent coronary events have an expansion of a distinctive T-cell subset, the CD4(+)CD28(null) T cells. These cells are highly inflammatory and cytotoxic in spite of lacking the costimulatory receptor CD28, which is crucial for optimal T cell function. The mechanisms that govern CD4(+)CD28(null) T cell function are unknown. OBJECTIVE Our aim was to investigate the expression and role of alternative costimulatory receptors in CD4(+)CD28(null) T cells in ACS. METHODS AND RESULTS Expression of alternative costimulatory receptors (inducible costimulator, OX40, 4-1BB, cytotoxic T lymphocyte associated antigen-4, programmed death-1) was quantified in CD4(+)CD28(null) T cells from circulation of ACS and stable angina patients. Strikingly, in ACS, levels of OX40 and 4-1BB were significantly higher in circulating CD4(+)CD28(null) T cells compared to classical CD4(+)CD28(+) T lymphocytes. This was not observed in stable angina patients. Furthermore, CD4(+)CD28(null) T cells constituted an important proportion of CD4(+) T lymphocytes in human atherosclerotic plaques and exhibited high levels of OX40 and 4-1BB. In addition, the ligands for OX40 and 4-1BB were present in plaques and also expressed on monocytes in circulation. Importantly, blockade of OX40 and 4-1BB reduced the ability of CD4(+)CD28(null) T cells to produce interferon-γ and tumor necrosis factor-α and release perforin. CONCLUSIONS Costimulatory pathways are altered in CD4(+)CD28(null) T cells in ACS. We show that the inflammatory and cytotoxic function of CD4(+)CD28(null) T cells can be inhibited by blocking OX40 and 4-1BB costimulatory receptors. Modulation of costimulatory receptors may allow specific targeting of this cell subset and may improve the survival of ACS patients. |
| Starting Page | 637 |
| Ending Page | 649 |
| Page Count | 13 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://circres.ahajournals.org/content/circresaha/110/6/857.full.pdf?download=true |
| PubMed reference number | 22282196v1 |
| Alternate Webpage(s) | https://doi.org/10.1161/CIRCRESAHA.111.261933 |
| DOI | 10.1161/CIRCRESAHA.111.261933 |
| Journal | Circulation research |
| Volume Number | 110 |
| Issue Number | 6 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Acute Coronary Syndrome Angina Pectoris Atherosclerosis Biomarkers, Tumor CD4 Positive T Lymphocytes Cell physiology Interleukin-2 Leukemia, B-Cell Ligands Necrosis Neoplasms OX40 Receptors Patients Plaque, Atherosclerotic Senile Plaques Subgroup T-Lymphocyte Subsets TNFRSF9 gene cellular targeting perforin |
| Content Type | Text |
| Resource Type | Article |
