Premature CD4~+T Cells Senescence In The Elderly With Cardiovascular Diseases

With the social and economic development of China, the level of population aging has been increasing, and the age-related diseases such as cardiovascular and cerebrovascular diseases, diabetes, cancer, infections and autoimmune diseases are commonly seen in the elderly, which has become the focus on social development issues. However, the pathogenesis of age-related diseases is not fully understood, and lacking effective means of prevention and treatment. In recent years, a growing number of studies have shown that immunosenescence-mediated disturbance is an important factor for the occurrence of cardiovascular disease, cancer, infection and other age-related diseases. Our previous study found that the presence of excessive activation of Killing T lymphocytes and regulatory T cell function defects in patients with acute coronary syndrome, T lymphocyte dysfunction and immune inflammatory effect induced instability and progress of atherosclerotic plaque. In addition, research suggests that the incidence of diabetes, hypertension and other common diseases of the elderly is closely related to the body’s immune abnormalities. Therefore, this study intends to from the view of immunosenescence, explore the role of CD4+T lymphocyte subtypes in the pathogenesis of acute coronary syndrome, diabetes and hypertension in elderly patients, and the correlation with chronic infection and inflammation. Part IPremature CD4+T cells senescence in patients with acute coronary syndromeObjectives Acute coronary syndrome is a complication of atherosclerotic vascular disease, which is a chronic inflammatory disease involving both innate and acquired immune responses. Acquired immune responses mediated by CD4+T cells contribute to the initiation and progression of this disease. Patients with acute coronary syndrome show acquired immune system abnormalities that resemble the characteristics of autoimmune dysfunction described in the elderly. In this study, we investigated whether patients with acute coronary syndrome have premature CD4+T cells senescence, and its potential causes.Methods The percentage of CD4+T lymphocyte subsets (naive T cells, regulatory T cells, memory T cells and effector T cells) were analyzed by multiple-color flow cytometry. The frequency of T cell receptor excision circles was quantitated using real-time PCR. The serum levels of C-reactive protein, Cytomegalovirus IgG, Helicobactor pylori IgG and Chlamydia pneumonia IgG were measured by ELISA. We evaluated15young healthy volunteers,20older healthy volunteers, and25age-matched patients with acute coronary syndrome.Results Acute coronary syndrome patients showed an expansion of CD4+CD28null effector T cells, a decline of CD4+CD25+CD62L+Treg cells, an accelerated loss of CD4+CD45RA+CD62L+naive T cells and a compensatory increase in the number of CD4+CD45RO+memory T cells. Acute coronary syndrome patients demonstrated no significant difference in frequency of T cell receptor excision circles compared to age-matched healthy volunteers. The percentage of CD4+T cell subpopulations correlated with chronic infection, which is a factor contributing to1mmunosenescence. Conclusions Premature CD4+T cell senescence closely correlated with chronic infection and may contribute to the development of acute coronary syndrome. PartⅡCostimulatory molecules and inflammatory indicator in diabetes and non-diabetes acute coronary syndrome patientsObjective To evaluate the frequency of CD4+CD28null T lymphocyte and C-reactive protein concentration in diabetes and non-diabetes coronary patients.Methods51coronary patients were divided into diabetes (n=21) and non-diabetes (n=30) group, according to the diagnostic standards of type2diabetes mellitus. Frequency of CD4+CD28null T lymphocyte was analysed by multiple-color flow cytometry and serum C-reactive protein (CRP) concentration was measured by ELISA, and the clinical information was recorded in these patients.Results Compared to the non-diabetes ACS patients, the frequency of CD4+CD28null T lymphocyte in peripheral blood of diabetes ACS patients increased (p<0.05), serum CRP concentration showed no significant difference (p>0.05), angiography results suggested that the rate of complete obstruction and diffuse pathogenic change in diabetes ACS patients were much higher (p<0.05).Conclusion Coronary pathogenic changes is more severe in diabetes ACS patients than pure ACS patients, and costimulatory molecule may involve in the immune-modulation disturbance of patients with diabetes and ACS. PartⅢThe expression of surface antigens on T lymphocytes in the peripheral blood of elderly hypertension patientsObjective To explore the expression of surface antigens CD45RA/RO on T lymphocytes and the relation with hypertension in the elderly.Methods Mononuclear cells were separated from the peripheral of20adult controls,25elderly controls and19hypertension patients aged more than60years old, and the frequencies of CD45RA+and CD45RO+T lymphocytes were analysed by flow cytometry.Results The frequency of CD45RA+in CD4+T lymphocytes of elderly control is decreased than that of the adult control, with a compensatory increase of the frequency of CD45RO+T lymphocytes; contrast to that of the elderly control group, the frequency of CD45RO+in CD4+T lymphocytes of elderly hypertension patients was significantly increased, and the ratio of CD45RA+to CD45RO+was significantly decreased (P<0.05respectively).Conclusions The expression shift of surface antigen CD45on T lymphocyte suggested that the activation and differentiation of T lymphocyte might closely associated with the occurrence of hypertension in the elderly.