Influence of Treg cells and HBV genotype on sustained response and drug resistance in the treatment with nucleoside drugs

We aimed to investigate the influence of regulatory T cells including CD4+CD25+, CD8+CD28- and hepatitis B virus (HBV) genotype on sustained virological response and tolerance of nucleoside drugs. One hundred and thirty-seven patients were enrolled. Lamivudine was administered to 84 patients. Entecavir was administered to the other 53 patients. Before treatment, biochemical tests, HBV DNA load, HBV serum level, HBV genotype, PB CD3+, CD4+, CD8+, CD4+CD25+/CD3+, and CD8+CD28-/CD3+ frequencies were measured. Based on HBV DNA loads after 4 weeks of therapy, patients were divided into response group and suboptimal response group. The lamivudine group received treatment continuously, and then patients were categorized into non-resistance group and resistance group. Compared with the suboptimal response and resistance groups for lamivudine, CD4+CD25+/CD3+ levels were higher in the response and non-resistance groups (t=4.372, P=0.046; t=7.262, P=0.017). In the non-resistance group, CD8+CD28-/CD3+ frequency was lower than in the resistance group (t=5.527, P=0.037). Virus load and hepatitis B E antigen (HBeAg)-positive rate were significantly lower than in the response and resistance group (t=2.164, P=0.038; X2=4.239, P=0.040; t=2.015, P=0.044; X2=16.2, P=0.000). Incidence of drug resistance was high in patients with virogene type C. For the virological response to entecavir, CD8+CD28-/CD3+ level was significantly lower than that of the suboptimal response group (t=6.283, P=0.036). Response and suboptimal response groups were compared in CD3+, CD4+, CD8+, CD4+CD25+/CD3+ and virus genotype, and differences were not statistically significant (P>0.05). Baseline regulatory T cells including CD4+CD25+/CD3+ and CD8+CD28-/CD3+ frequencies have a relationship with the incidence of rapid virological response and the resistance to nucleoside drugs. Patients with HBV genotype C receiving lamivudine more often underwent drug resistance. Antiviral efficacy and the resistance to lamivudine were closely correlated with baseline factors; the same cannot be found for entecavir.

The immunoregulatory effect of CD8+CD28-T lymphocytes in an experimental bone marrow mesenchymal stem cell treatment of autoimmune encephalomyelitis / 中华物理医学与康复杂志

Objective To study the immune system regulatory effects of CD8+CD28-regulatory T lymphocytes in an experimental bone marrow mesenchymal stem cell treatment of autoimmune encephalomyelitis.Methods A model of autoimmune encephalomyelitis (EAE) was established in twenty-eight C57BL/6 female mice,6 to 8 weeks old weighing 16 to 20 g using myelinoligodendrocyte glycoprotein 35-55 amino acid peptide (MOG35-55).The mice were randomly divided into a phosphate-buffered solution (PBS) group (n =7),an MSCs-Low group [n =7 which received an injection of 2× 105 mesenchymal stem cells (MSCs)],an MSCs-Med group (n=7,1× 106 MSCs),and an MSCs-High group (n=7,5×106 MSCs).Their clinical condition was then evaluated daily.On the 15th day after the MOG35-55 immunization,the different MSC doses were administered intravenously via the tail.On the 30th day the mice were sacrificed to observe any neuropathology of the spinal cord.At the same time,FACS flow cytometry was used to assay CD8+CD28-T cells in the spleen.Results Compared with the PBS control group,the MSC treatment effectively alleviated illness among the mice by the 15th day after the immunization.The maximum and average disease scores and clinical illness scores had all improved significantly.The medium dosage worked best.Neuropathological analysis showed that the MSC treatment could significantly reduce the invasion of inflammatory cells and minimize demyelination in the spinal cord.Furthermore,the CD8+ CD28-regulatory T cells in the spleens of the MSCtreated animals increased compared with the PBS control group,though the secreted levels of IL-10 showed no obvious difference.Conclusions Treatment with MCSs can promote the recovery of neural function in autoimmune encephalomyelitis,at least in mice.CD8+CD28-regulatory T cells may not be the main effector cells,playing only a synergistic therapeutic role.

CD8+T cells in peripheral blood of patients with acute antituberculosis drug-induced liver injury on the expression and significance of CD28 / 上海预防医学

Objective ] To detect the percentage of CD8+CD2-8、CD8+CD2+8 cells in patients with antituberculosis drug-induced liver injury and investigate their expression on acute liver injury by antituberculosis drugs and clinical significance. [ Methods] The flow cytometry was used to detect the percentages of CD8+CD2-8 and CD8+CD2+8 in peripheral blood of 42 patients with antituberculosis drug-induced acute liver injury, and 232 normal liver function patients with antituberculosis treatment.The mean amount of T cells between the two groups were compared by t-test and when P <0 .05 the difference found in comparison was thought to be statistically significant. [ Results] The percentage of CD8+CD2-8 cells of antituberculosis drug-induced acute injury group was lower than that of antituberculosis with normal liver function group (12.2 ±7.7%and 23.6 ±10.4%) , and the difference was of statistical significance ( t=4.782,P<0.01).And the amount of CD8+CD2+8 cells in antituberculosis drug-induced acute injury group was higher than that in antituberculosis with normal liver function group ( 23.5 ±9.1% and 10.2 ± 6.7%), the difference being statistically significant (t=5.356,P<0.01) too. [Conclusion] The amount of CD8+CD2-8 cells is reduced in peripheral blood of patients with antituberculosis drug-induced acute injury, while the amount of CD8+CD2+8 cells is increased.It is held that CD28 expression on CD8+T cells can be used as a marker of immunological detection in antituberculosis drug-induced acute liver injury.

Change and significance of the regulatory T lymphocytes expression in rats model of chronic abacterial prostatitis / 中华泌尿外科杂志

Objective To investigate the change and significance of regulatory T lymphocytes in peripheral blood of rats model of chronic abacterial prostatitis.Methods Twelve Wistar rats with weight of approximate 390 g were randomly divided into two groups,model group and control group.Rats in the model group was injected subcutaneously 17β-estradiol(0.25 mg/day,for 30 days) after castration to establish rat model of chronic abacterial prostatitis.Flow cytometry was applied to detect the frequency of CD+4 CD+25 cells and CD+8CD-28 cells in peripheral blood of rats after model establishment.Results Compared with control group (11.63±1.36)％,the proportion of CD+4 CD+25T lymphocytes in model group (7.90±1.74)％ significanlty decreased (P＜0.01).Compared with control group (24.64±4.76)％,the proportion of CD+8CD-28T lymphocytes in model group (17.18±2.83) ％ also significantly decreased (P＜0.01).Conclusions The changes of the ratio of CD+4 CD+25T lymphocytes and CD+8CD-28T lymphocytes in peripheral blood of rats model of chronic abacterial prostatitis provided evidences for pathogenic mechanism of regulatory T lymphocytes participating in the development of chronic abacterial prostatitis.

Circulating CD4~+CD25~+ and CD8~+CD28~- T regulate cells in multiple myeloma / 中国免疫学杂志

Objective: The study was designed to evaluate the changes and significance of circulating CD4~+CD25~+ and CD8~+CD28~- regulatory T cells (Tregs) in patients with multiple myeloma (MM).Methods:CD4~+CD25~+ and CD8~+CD28~-Tregs in peripheral blood of 38 patients with MM and of 20 healthy doners were measured by flow cytometry.Serum albumin and β_2-MG in patients with MM were measured using bromocresol green method,transmission turbidimetry respectively.Results:Compared to those of the controls,the proportions of CD4~+CD25~(+/high),CD4~+CD25~(high) CD127~(low) and CD8~+CD28~-Treg cells in newly diagnosed MM patients were elevated.Furthermore,the proportions of CD4~+CD25~(high) and CD4~+CD25~(high)CD127~(low) Tregs in each clinical stage were elevated when compared to those of the controls.The number of the Tregs were increasing with clinical stages and were significantly higher in stage Ⅲ MM than in stageⅠ MM;In stageⅡand Ⅲ MM,there were also elevated proportions of CD8~+CD28~- Tregs,increasing with clinical stages.However,there were no differences when compared between stage Ⅰ MM and the controls;Both the proportions of CD4~+CD25~(+/high) and CD4~+CD25~(high)CD127~(low) Tregs in active MM were not different from stable MM,although all of them were higher than those of controls.The proportion of CD8~+CD28~- Tregs was higher in active MM than in stable MM and controls,but there were no differences when compared between active and stable MM.The proportions of both CD4~+CD25~(high) Tregs and CD4~+CD25~(high)CD127~(low)Tregs had negative correlation with the levels of serum albumin.Conclusion:MM patients have elevated levels of circulating CD4~+CD25~+ and CD8~+CD28~-Tregs,which may be an important mechanism of MM immune evasion,and may be associated with clinical stages,disease progression and prognosis of MM to some extent.

The induction of CD8+CD28- regulatory T cells by donor specific transfusion and their effect on the acute rejection responses in rats liver transplantation / 中华微生物学和免疫学杂志

Objective To acquire antigen specific CD8+CD28-Tr by donor specific transfusion (DST) in vivo, and evaluate their suppressive effect on the acute rejection responses in rat liver transplantation through adoptive transfer experiment. Methods DST was used to induce CD8 + CD28 Tr to LEW antigens in naive Brown Norway(BN) rat. Then the induced CD8+CD28- Tr were adoptively transferred into the recipients of LEW→BN liver transplantation, which were acute rejection models. The survival time and histological changes were observed. Statistic analysis was performed with Log-Rank test by SPSS11.0 software, to compare the survival rate. Results Adoptive transfer of the DST-induced CD8+CD28-Tr attenuated the acute rejection responses in acute rejection models of rat liver transplantation. Conclusion DST can induce large numbers of CD8+CD28-Tr in naive BN rats in vivo. The adoptive transfer of the induced CD8+CD28Tr suppressed the acute rejection responses in rat liver transplantation. DST may become one of the methods that induce antigen specific CD8+CD28- Tr in vivo.

Analysis of T lymphocyte subsets in patients with primary biliary cirrhosis / 中华风湿病学杂志

Objective To investigate the significance and characteristics of T lymphocyte subsets and co-stimulatory CD28 in peripheral blood of patients with primary biliary cirrhosis. Methods Tri-colour flow-cytometry was used to detect the levels of T lymphocyte subsets in peripheral blood in 98 patients with primary biliary cirrhosis and 30 age and gender matched healthy controls. Results Compared to control group the percentage of CD4+ T increased and CD8+ T lymphocyte decreased in the PBC group. The CD4+/CD8+ ratio in the PBC group was higher than that in the control group (P<0.05). And the percentage of CD4+CD28- T cells and CD8+CD28- T cells increased, too (P<0.05). Conclusion There are immunological abnormalities in PBC and the expression of co-stimulator CD28 is significantly decreased. CD8+CD28-T lymphocytes may have immune regulatory effect in PBC.

Studies of the expression of CD40~+、CD40L~+ and CD8~+/CD28~+ on peripheral blood cells in patients with chronic B hepatitis / 中国免疫学杂志

0.05).There was a positive corrlation on CD40~+ and CD40L~+ in chronic B hepatitis patients.There was a positive corrlation on CD8~+/CD28~+ and CD40~+、CD40L~+ in chronic B hepatitis patients.There were no remarkable corrlation on CD8~+/CD28~- and CD40~+、CD40L~+ in chronic B hepatitis patients.Conclusion:The costimulation molecules CD40~+、CD40L~+ and CD8~+/CD28~+ are lower,while CD8~+/CD28~- are higher in chronic B hepatitis patients than in the health.To test the expression of CD40~+、CD40L~+ and CD8~+/CD28~+ on peripheral blood of the chronic B hepatitis could help to evaluate patients's celluar immunity and guide clinical treatment.