Abstract
Acquired immune responses mediated by CD4+ T cells contribute to the initiation and progression of acute coronary syndrome (ACS). ACS patients show acquired immune system abnormalities that resemble the characteristics of autoimmune dysfunction described in the elderly. This study aimed to investigate the role of premature CD4+ T cells senescence in ACS and the underlying mechanism. We compared the immunological status of 25 ACS patients, 15 young healthy individuals (C1), and 20 elderly individuals with absence of ACS (C2). The percentages of CD4+ T lymphocyte subsets (including naïve, regulatory, memory and effector T cells) in peripheral blood were analyzed. In ACS patients, a significant expansion of CD4+CD28null effector T cells and a decline of CD4+CD25+CD62L+Treg cells were observed. In addition, patients with ACS showed an accelerated loss of CD4+CD45RA+CD62L+ naïve T cells and a compensatory increase in the number of CD4+CD45RO+ memory T cells. ACS patients demonstrated no significant difference in frequency of T cell receptor excision circles (TRECs) compared to age-matched healthy volunteers. The expression of p16Ink4a was increased while CD62L was decreased in CD4+CD28null T cells of ACS patients. Compared to healthy donors, ACS patients demonstrated the lowest telomerase activity in both CD4+CD28+and CD4+CD28null T cells. The serum levels of C-reactive protein, Cytomegalovirus IgG, Helicobactor pylori IgG and Chlamydia pneumonia IgG were significantly higher in ACS patients. The results suggested that the percentage of CD4+ T cell subpopulations correlated with chronic infection, which contributes to immunosenescence. In conclusion, chronic infection induced senescence of premature CD4+T cells, which may be responsible for the development of ACS.
Highlights
Acquired immune responses mediated by CD4+ T cells contribute to the initiation and progression of acute coronary syndrome (ACS)
Consistent with the published data[11], our results showed that the CD3+CD4+CD28null T cell subset was rarely observedin healthy young controls, with a frequency of 1.6 ±1.3% of CD3+CD4+ T lymphocytes
We found that C-reactive protein (CRP) levels were significantly higher in serum from the groups of aged healthy donors and ACS patients compared to those from the group of young healthy donors (Table 3).higher levels of serum IgG antibodies against CMV, Helicobactor pylori (HP), and Chlamydia pneumonia (Cpn) were detected in patients with ACS (Table 3)
Summary
Acquired immune responses mediated by CD4+ T cells contribute to the initiation and progression of acute coronary syndrome (ACS). ACS patients show acquired immune system abnormalities that resemble the characteristics of autoimmune dysfunction described in the elderly. The decline in the output of new cells from the thymus, low numbers of naïve T cells, and compensatory increasing of memory T cells in the peripheral blood of the elderly are generally considered hallmarks of immunosenescence. Infectious agents, such as stimulating antigens, contribute to the persistent activation of T cells and the production of autoimmune antibodies. Our results show that dysfunction of immune system is involved in the pathogenesis of ACS
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