High levels of costimulatory receptors OX40 and 4-1BB characterize CD4+CD28null T cells in patients with acute coronary syndrome
| Autor: | Juan Carlos Kaski, Pitt Lim, Caroline J. Finlayson, Nicholas Bunce, Ian M. Loftus, Ingrid E. Dumitriu, Ricardo F. Antunes, Paramita Baruah |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
CD4-Positive T-Lymphocytes
Male Acute coronary syndrome Physiology T cell Coronary Artery Disease Biology Ligands Cell Degranulation Granzymes Interleukin 21 Tumor Necrosis Factor Receptor Superfamily Member 9 Immune system CD28 Antigens medicine Cytotoxic T cell Humans Acute Coronary Syndrome Receptor Antigen-presenting cell Aged Aged 80 and over Perforin CD28 Middle Aged Receptors OX40 medicine.disease CD4 Lymphocyte Count medicine.anatomical_structure Immunology CD4 Antigens Female Cardiology and Cardiovascular Medicine Signal Transduction |
| Zdroj: | Circulation research. 110(6) |
| ISSN: | 1524-4571 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|