| AIDS(acquired immune deficiency syndrome), an infectious disease with high fatality and propagation speed, is caused by HIV and characterized by total collapse of human immune system. HIV itself will not cause any disease. However, when CD4+ T lymphocytes that play a coordinating role in the immune system are damaged by HIV and drop dramatically in quantity, the human body will infect other diseases due to deficiency of resistance and even die. Clinically, patients’ resistant ability to disease is gradually decreased, and the patients will die of one or several kinds of opportunistic infections disease or cancer.In the immune system, CD4+CD25+regulatory T cells can regulate innate and acquired immune system function and control the overgrowth of T cells that is the respond to autoantigen reactivation by direct contact with cells, cytokine secretion and other mechanisms, so they play an important role in maintaining immune tolerance and homeostasis. During HIV, continuous antigenic stimulation, tissue damage, generation of immature DC, etc. can induce the generation of CD4+CD25+regulatory T cells, thus affecting the immune response of human body to HIV. Studies have shown that HIV infection can lead to the change of CD4+CD25+regulatory T cells in quantity.PD-1/PD-L mediated negative synergy stimulus signal, mainly expressed on the surface of T, B and mononuclear lymphocytes, plays the inhibitory role on immune function. It has been found that the T cell activation must receive synergy stimulus signal while stimulated by antigen signals. Positive and negative synergy stimulus signals received by immune cells need achieve a relative balance so the immune response can start and end properly. Negative signals mediated by PD-1/PD-L can effectively inhibit the functions of T and B cells and play a vital role in negativeregulation in the late period of human immune response, which are of important biological significance in tumor immunity, autoimmunity, transplantation immunity and infectious disease.This research explored the correlation between in vivo CD3+T cells, CD4+ T cells,CD8+T cells and CD4+CD25+Treg proportion, the quantity of CD4+T cells and the probability of HIV infection and disease progression through analysis on expressions of regulatory T cells in peripheral blood of AIDS patients and correlation research based on absolute quantity of CD4+T cells. At the same time, immunofluorescence and monoclonal antibody labeling were used to analyze the expression characteristics of PD-1 on surface of peripheral lymphocytes so as to discuss the biological significance of this negative synergy stimulus molecule in medication of immune function in AIDs patients.Objective: To analyze the changes of CD4+CD25+highregulatory T cells in peripheral blood of HIV/AIDS patients; to explore its correlation with absolute quantity of CD4+ T cells and with probability of HIV infection and disease progression; to analyze the expression characteristics of PD-1 molecules in peripheral blood of HIV/AIDS patients; to discuss the biological significance of this negative synergy stimulus molecule in medication of immune function in AIDs patients.Methods: A total of 100 patients with HIV infection were selected as the research objects, while 20 cases of healthy blood donators were selected as the controls.Immunofluorescence and monoclonal antibody labeling were used to detect the expression of CD3+T cells, CD4+ T cells, CD8+ T cells and regulatory T cells in AIDS patients. The percentages of lymphocytes to the total lymphocytes of different groups were compared. And the patients were grouped according to the absolute value of CD4+T cells. The expression characteristics of CD4+CD25+high and CD4+PD-1+ were analyzed to discuss the correlation between in vivo Treg proportion, the quantity of CD4+T cells and the probability of HIV infection and disease progression and to discuss the biological significance of this negative synergy stimulus molecule- PD-1 on the surface of peripheral blood of AIDS patients- in medication of immune function in AIDs patients.Results:(1) Peripheral T cell subgroup was disorderly expressed in patients with HIV infection: flow cytometry showed the expressions of CD3+and CD8+T cells were significantly higher than that of the healthy control group, and the expressions of CD4+T cells were significantly lower than that of the healthy controls; And there were significant differences in lymphocytes CD4+and CD8+T cells compared with the control group, and there were no significant differences in lymphocytes CD3+ T cells compared with the control group(p=0.4528); Similarly, there were significant differences between T cells and the control group in expression of CD4+and CD8+T cells.(2) Groups with different absolute values of CD4 had different expressions of T subgroups: there were no significant differences between groups with absolute value of CD4<200/ul,200-500/ul and >500/ul in expression of CD3+T cells; expressions of CD4+and CD8+T cell subgroups were different among lymphocytes of three groups; there were significant differences between groups with absolute value of CD4<200/ul and >500/ul as well as between groups with CD4 of 200-500/ul and >500/ul; there were no significant differences between groups with absolute value of CD4<200/ul and200-500/ul in expression of CD4+ and CD8+T cell subgroup in lymphocytes.(3)Peripheral CD4+PD-1+T cell and CD4+CD25+Treg showed significantly high expression in AIDS patients: AIDS patients showed significantly high expression of peripheral CD4+ and CD8+T cells, which were significantly different with the control group; there was also obvious difference compared with the control group in CD4+PD-1+high; and Treg was significantly higher in the detection group than the control group. CD4+PD-1+of the group with absolute value of CD4 <200/ul and 200-500/ul was all higher than that of the group with absolute value of CD4 >500/ul. There were significant differences between the group with absolute value of CD4 <200/ul and 200-500/ul as well as >500/ul group in Treg. There was a negative correlation between CD4+PD-1+T cells and CD4+CD25+highTreg expression as well as the absolute value of CD4. The results showed abnormal expression of peripheral lymphocyte subsets, Treg and PD-1 in AIDS patients, and the cell immune function was disordered, which were closely related with disease progress of patients with HIV infection.Conclusions: In patients with HIV/AIDS, the proportion of CD4+CD25+highregulatory T cells in peripheral blood was related to the absolute number of CD4+T cells.The increased proportion of Treg in patients is an important cause leading to deficiency of CD4+T, the increased rate of HIV infection and disease progression. In addition, the further analysis showed that the negative stimulus molecule PD-1 was also obviously correlated with the expression of CD4+T and the absolute number of CD4+T cells, thus revealing the increased expression of PD-1 is another important factor in inhibition of CD4+ T. In conclusion, the expressions of CD4+CD25+ Treg and PD-1 are increased on CD4+T, which are negatively correlated with the absolute value of CD4+T in the peripheral blood of HIV/AIDS patients. This may be an important factor leading to the increased risk of infection and affecting disease progression. |
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