Persistent accumulation of interferon-γ-producing CD8+CD56+ T cells in blood from patients with coronary artery disease

Age-related changes in the immune system, commonly termed "immunosenescence," contribute to deterioration of the immune response and fundamentally impact the health and survival of elderly individuals. Immunosenescence affects both the innate and adaptive immune systems; however, the most notable changes are in T cell immunity and include thymic involution, the collapse of T cell receptor (TCR) diversity, an imbalance in T cell populations, and the clonal expansion of senescent T cells. Senescent T cells have the ability to produce large quantities of proinflammatory cytokines and cytotoxic mediators; thus, they have been implicated in the pathogenesis of many chronic inflammatory diseases. Recently, an increasing body of evidence has suggested that senescent T cells also have pathogenic potential in cardiovascular diseases, such as hypertension, atherosclerosis, and myocardial infarction, underscoring the detrimental roles of these cells in various chronic inflammatory responses. Given that cardiovascular disease is the number one cause of death worldwide, there is great interest in understanding the contribution of age-related immunological changes to its pathogenesis. In this review, we discuss general features of age-related alterations in T cell immunity and the possible roles of senescent T cells in the pathogenesis of cardiovascular disease.

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“…CD56 ? T cells in the peripheral blood of patients with acute coronary syndrome and angina [72]. In addition, CD4 ?…”

Section: Senescent T Cells In Atherosclerosis and Coronary Artery Dismentioning

confidence: 99%

T cell senescence and cardiovascular diseases

Park

Shin

et al. 2015

Clin Exp Med

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“…[10][11][12][13] An expansion of CD28 -CD57 + CD8 + T cells has also been described in patients with coronary artery disease compared with healthy individuals. 14,15 Finally, CD8 + T-lymphocyte depletion by anti-CD8 mAb in apoE-deficient mice fed a high-fat diet ameliorates atherosclerosis and infusion of CD8 + T lymphocytes promotes the development of vulnerable atherosclerotic plaques in lymphocyte-deficient apoE 2/2 mice. 16 Such T cells produce high amounts of proinflammatory cytokines, including IFN-g and TNF-a.…”

Section: Discussionmentioning

confidence: 99%

Polyclonal Antithymocyte Globulin and Cardiovascular Disease in Kidney Transplant Recipients

Ducloux¹,

Courivaud

Bamoulid

et al. 2014

Journal of the American Society of Nephrology

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T-lymphocyte activation may contribute to atherosclerosis, the prevalence of which is increased in transplant patients. However, the cardiovascular consequences of polyclonal antithymocyte globulin (ATG)-induced immune modifications, which include alterations in T-cell subsets, are unknown. We conducted a retrospective single-center study to assess whether ATG associates with an increased incidence of atherosclerotic events (CVEs) in kidney transplant patients. Propensity score analysis was performed to address potential confounding by indication. We also tested whether ATG use induces a proatherogenic immune status. Sixty-nine (12.2%) CVEs occurred during follow-up (87631 months). The cumulative incidence of CVEs was higher in ATG-treated patients (14.7% versus 8.2%; P=0.03). Cox regression analysis revealed that ATG use was an independent risk factor for CVEs (hazard ratio [HR], 2.36; 95% confidence interval [95% CI], 1.35 to 4.13; P=0.003). Results obtained in the propensity score match analysis recapitulated those obtained from the overall cohort (HR, 2.09; 95% CI, 1.11 to 3.98; P=0.02). Late-stage differentiated CD8 + T cells increased 1 year after transplantation only in ATG-treated patients. More generally, ATG associated with features of immune activation. These modifications increased markedly in patients exposed to cytomegalovirus (CMV). Subanalyses suggest that the effect of ATG on CVEs is restricted to CMV-exposed patients. However, CMV infection associated significantly with CVEs only in ATG-treated patients (HR, 2.07; 95% CI, 1.16 to 3.70; P=0.01). In conclusion, ATG associated with both immune activation and post-transplant CVEs in this cohort. Further studies should precisely determine whether ATG-induced immune activation is the causal link between ATG and CVEs.

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“…We have shown the infiltration of CD56 + CD28 null CD4 + T cells in extra-articular lesions in rheumatoid arthritis (182). Inflammatory CD56 + T cells have been reported in coronary artery disease, asthma, ulcerative colitis, and chronic hepatitis C disease (183–186). NKG2D + CD28 null T cells have some tumor-promoting activity in experimental settings (187, 188) and as inflammatory mediators in Wegener’s granulomatosis, rheumatoid arthritis, juvenile-onset systemic lupus erythematosus, and celiac disease (189–192).…”

Section: Nk-like T Cells In Young Persons With Chronic Diseases: a Camentioning

confidence: 99%

Functionally Diverse NK-Like T Cells Are Effectors and Predictors of Successful Aging

2016

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The fundamental challenge of aging and long-term survivorship is maintenance of functional independence and compression of morbidity despite a life history of disease. Inasmuch as immunity is a determinant of individual health and fitness, unraveling novel mechanisms of immune homeostasis in late life is of paramount interest. Comparative studies of young and old persons have documented age-related atrophy of the thymus, the contraction of diversity of the T cell receptor (TCR) repertoire, and the intrinsic inefficiency of classical TCR signaling in aged T cells. However, the elderly have highly heterogeneous health phenotypes. Studies of defined populations of persons aged 75 and older have led to the recognition of successful aging, a distinct physiologic construct characterized by high physical and cognitive functioning without measurable disability. Significantly, successful agers have a unique T cell repertoire; namely, the dominance of highly oligoclonal αβT cells expressing a diverse array of receptors normally expressed by NK cells. Despite their properties of cell senescence, these unusual NK-like T cells are functionally active effectors that do not require engagement of their clonotypic TCR. Thus, NK-like T cells represent a beneficial remodeling of the immune repertoire with advancing age, consistent with the concept of immune plasticity. Significantly, certain subsets are predictors of physical/cognitive performance among older adults. Further understanding of the roles of these NK-like T cells to host defense, and how they integrate with other physiologic domains of function are new frontiers for investigation in Aging Biology. Such pursuits will require a research paradigm shift from the usual young-versus-old comparison to the analysis of defined elderly populations. These endeavors may also pave way to age-appropriate, group-targeted immune interventions for the growing elderly population.

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Persistent accumulation of interferon-γ-producing CD8+CD56+ T cells in blood from patients with coronary artery disease

Cited by 56 publications

References 31 publications

T cell senescence and cardiovascular diseases

T cell senescence and cardiovascular diseases

Polyclonal Antithymocyte Globulin and Cardiovascular Disease in Kidney Transplant Recipients

Functionally Diverse NK-Like T Cells Are Effectors and Predictors of Successful Aging

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