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De novo expression of killer immunoglobulin-like receptors and signaling proteins regulates the cytotoxic function of CD4 T cells in acute coronary syndromes.
Abstract
The inflammatory infiltrate in atherosclerotic plaque is composed of T cells and macrophages. CD4 + T cells with a unique phenotype, CD4 + CD28 null , are preferentially recruited into culprit lesions. These T cells are distinct from classic CD4 + CD28 + T cells in gene expression and function, including their ability to mediate cytolysis. In this study, we have investigated the regulation of CD4 + CD28 null T-cell cytolytic function. In patients with acute coronary syndromes (ACS), CD4 + CD28 null T cells express killer immunoglobulin-like receptors (KIRs). KIRs encompass a polymorphic family of receptors that recognize HLA class I molecules and have been implicated in self-tolerance. CD4 + CD28 null T-cell clones from patients with ACS and age-matched controls were compared for their KIR-expression profile. T-cell clones derived from the patients expressed a broader spectrum of KIRs ( P <0.001) with preference for the stimulatory variant, CD158j. Additionally, CD4 + T-cell clones from patients but not those from controls acquired de novo expression of the DAP12 molecule, an adapter chain that transmits CD158j-derived signals. Cumulative expression of CD158j and DAP12 endowed cytolytic competence on CD4 + CD28 null T cells, allowing them to kill in the absence of T-cell receptor triggering. Our data demonstrate that CD4 + CD28 null T cells in ACS are characterized by a unique gene expression profile. Consequently, these T cells acquire cytolytic capability that can bypass the need for T-cell receptor triggering and, thus, impose a threat to self-tolerance.
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“CD28− T cells are high producers for interferon-γ (IFN-γ), display cytotoxic functions and accumulate in inflammatory lesions [21–26].”
From T-cell aging in rheumatoid arthritis (2014) · cites this paper as [25]
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Metadata
- Authors
- Nakajima, T., Goek, O., Zhang, X., Kopecky, S. L., Frye, R. L., Goronzy, J. J., & Weyand, C. M.
- Affiliations
- Mayo Clinic (US)
- From the Departments of Medicine (T.N., O.G., X.Z., S.L.K., R.L.F., J.J.G., C.M.W.) and Immunology (J.J.G., C.M.W.), Mayo Clinic, Rochester, Minn.
- Venue
- Circulation Research
- Published
- 2003-07-25
- Volume
- 93
- Issue
- 2
- Pages
- 106-113
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- OpenAlex
- W2114639295
- Cited by
- 127
- References
- 44
- Citations by year
- 2026: 2 · 2024: 1 · 2023: 1 · 2022: 4 · 2021: 4 · 2020: 3 · 2019: 2 · 2017: 3 · 2016: 6 · 2015: 2 · 2014: 4 · 2013: 5 · 2012: 6
- FWCI
- 3.46
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Mayo Foundation for Medical Education and Research (R01 AR42527, R01 AR41974)
- National Institutes of Health
- National Heart, Lung, and Blood Institute (R01HL063919, R01 HL 63919)
- National Eye Institute (R01EY011916, R01 EY 11916)
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR041974, R01 AR 41974, R01AR042527, R01AR42527)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Keywords
- killer cell immunoglobulin-like receptors, CD4+CD28null T cells, acute coronary syndrome, DAP12, T cell cytotoxicity, atherosclerosis, self-tolerance, inflammatory cell infiltration
- MeSH terms
- Acute Disease, Aged, Arteriosclerosis, Cells, Cultured, Clone Cells, Coronary Disease, Cytotoxicity Tests, Immunologic, Female, Flow Cytometry, Multigene Family, Humans, Male, Membrane Proteins, Proteins, Receptors, Immunologic, T-Lymphocytes, Cytotoxic, Signal Transduction, CD4-Positive T-Lymphocytes, T-Lymphocyte Subsets, CD28 Antigens, Protein Isoforms, Adaptor Proteins, Signal Transducing, Receptors, KIR
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