High levels of costimulatory receptors OX40 and 4-1BB characterize CD4+CD28null T cells in patients with acute coronary syndrome.
Circ Res
; 110(6): 857-69, 2012 Mar 16.
Article
em En
| MEDLINE
| ID: mdl-22282196
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 ANDRESULTS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Linfócitos T CD4-Positivos
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Transdução de Sinais
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Membro 9 da Superfamília de Receptores de Fatores de Necrose Tumoral
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Receptores OX40
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Síndrome Coronariana Aguda
Limite:
Aged
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Aged80
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Circ Res
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Reino Unido