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Senescent cytotoxic T cells in acute myocardial infarction: innocent bystanders or the horsemen of apocalypse?

Cellular & Molecular Immunology volume 12, pages 510–512 (2015)Cite this article

Progressive deterioration of innate and adaptive immune functions, a status termed ‘immunosenescence’, is associated with the higher frequency and severity of diseases in the elderly, such as chronic infections, cancer and autoimmune disorders.1 Age-related immunosenescence can be characterized by a decrease in adaptive immunity and increase in low-grade chronic inflammation, also referred to as ‘inflamm-aging’.2 This dysfunctional immunity is characterized by perturbations of the T-lymphocyte compartment, largely attributed to thymus involution, shrinkage of the naive T-cell repertoire and oligoclonal expansions of memory T cells, particularly of CD8+ effector memory subsets.3 Age and latent viral infections, especially human cytomegalovirus (CMV), are both considered a driving force of CD8+ T-cell expansion and senescence, which is characterized by shortened telomeres, progressive loss of costimulatory receptors, CD28 and CD27, and expression of senescence-associated surface markers, such as KLRG1 and the glycoepitope CD57, which also reflects the proliferative history of cells.4

In this issue of the Journal, Yu and colleagues report on the association between the frequencies of circulating CD8+ T cells that express CD57 and the short-term cardiovascular mortality in patients following acute myocardial infarction. Using flow immunophenotyping and functional assays the authors characterized the CD8+CD57+ subset as differentiated, senescent-like, mostly CMV-reactive cytotoxic T cells. There are several limitations of this study. The primary endpoint (cardiovascular death) was only reached in seven patients, which makes the study underpowered and too small to draw definite conclusions. In part, this seems due to some selection process in choosing patients with relatively small infarcts, but mainly the overall small sample size of 58 patients. Another limitation is clearly the lack of distinction between CMV-seropositive and -seronegative patients. This would be important, since CMV-specific cells express high levels of CD57, and as is shown, CD8+CD57+ cells react to CMV-specific antigen stimulation by secretion of the pro-inflammatory cytokines TNF-α and IFN-γ. The authors assume, which is most plausible, that expansion of CD8+CD57+ T cells would most likely had occurred already long before the onset of myocardial infarction, indicating long-term immune activation or chronic low-grade inflammation in these patients. If this would be the case, then what is the likely mechanism behind the upregulation of CD57 on CD8+ T cells in these patients? It is conceivable that general chronic inflammation can drive T-cell proliferation and thereby CD57 expression simply as a marker of proliferation history of a cell, also reflected by short telomere length.4 In addition, CD57 also identifies a population of CMV-specific cytotoxic T cells, which can induce chemokine-mediated endothelial damage, potentially accelerating the progression of atherosclerosis.5

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Authors and Affiliations

  1. Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany

    Jedrzej Hoffmann

  2. Institute of Genetic Medicine, Newcastle University, Newcastle Upon Tyne, UK

    Ioakim Spyridopoulos

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  1. Jedrzej Hoffmann
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Correspondence to Ioakim Spyridopoulos.

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Hoffmann, J., Spyridopoulos, I. Senescent cytotoxic T cells in acute myocardial infarction: innocent bystanders or the horsemen of apocalypse?. Cell Mol Immunol 12, 510–512 (2015). https://doi.org/10.1038/cmi.2014.93

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