CXCR5+ CD4+ T cell subsets and their relationship to immune dysfunction in chronic hepatitis B-associated liver cirrhosis.

BACKGROUND AND AIM: Hepatitis B-associated liver cirrhosis (HBC) leads to profound alterations of immune systems, especially disruptions of B cell immune responses. CXCR5+ CD4+ T cells (including T follicular helper [Tfh] cells and T follicular regulatory [Tfr] cells) are responsible for the regulation of B cell functions. The aim of this study was to dissect the roles of CXCR5+ CD4+ T cell subset in B cell disruption caused by HBC. METHODS: Forty-one patients with HBC and 15 healthy controls were enrolled in this study. ELISA, flow cytometric analysis, and cell coculture were performed to analyze the properties of Tfh and Tfr. RESULTS: We observed significantly decreased memory B cells and increased plasma B cells in HBC patients, as well as significant upregulation of lipopolysaccharide binding protein and soluble CD14 in plasma of decompensated HBCs patients. The downregulation of Tfh17 was observed in HBC patients with spontaneous bacterial peritonitis compared with those without. The decrease of Tfh17 was paralleled with Child-Pugh grade and negatively correlated with plasma B cells and soluble CD14 in HBC patients. Interleukin (IL)-21+ Tfh of HBC patients was also downregulated compared with healthy controls, and it was positively correlated with memory B cells and the upregulation of IL-10+ Tfr. It was then revealed that Tfr could inhibit the secretion of IL-21 by Tfh, and the blocking of IL-10 could diminish this effect. CONCLUSIONS: The changes of the frequency and function of Tfh and Tfr may play an important role in disease progression and immune dysfunction of HBC.

Cross-sectional study of the relationship of peripheral blood cell profiles with severity of infection by adenovirus type 55.

BACKGROUND: The immunologic profiles of patients with human adenovirus serotype 55 (HAdV-55) infections were characterized in subjects diagnosed with silent infections (n = 30), minor infections (n = 27), severe infections (n = 34), and healthy controls (n = 30) during a recent outbreak among Chinese military trainees. METHODS: Blood was sampled at the disease peak and four weeks later, and samples were analyzed to measure changes in leukocyte and platelet profiles in patients with different severities of disease. Differential lymphocyte subsets and cytokine profiles were measured by flow cytometry and Luminex xMAP®, and serum antibodies were analyzed by ELISA and immunofluorescence staining. RESULTS: Patients with severe HAdV infections had higher proportions of neutrophils and reduced levels of lymphocytes (p < 0.005 for both). Patients with minor and severe infections had significantly lower platelet counts (p < 0.005 for both) than those with silent infections. The silent and minor infection groups had higher levels of dendritic cells than the severe infection group. Relative to patients with silent infections, patients with severe infections had significantly higher levels of IL-17+CD4+ cells, decreased levels of IL-17+CD8+ cells, and higher levels of IFN-γ, IL-4, IL-10, and IFN-α2 (p < 0.001 for all comparisons). CONCLUSIONS: Patients with different severities of disease due to HAdV-55 infection had significantly different immune responses. These data provide an initial step toward the identification of patients at risk for more severe disease and the development of treatments against HAdV-55 infection.

Preferential loss of Th17 cells is associated with CD4 T cell activation in patients with 2009 pandemic H1N1 swine-origin influenza A infection.

Very limited evidence has been reported on host T cell responses to the pandemic H1N1 swine-origin influenza A virus (S-OIV) infection in humans. Therefore, we investigated the proportions of peripheral T cell subsets and analyzed the relationship of T helper subset changes with T cell activation during this infection. We found that these S-OIV-infected patients exhibited rapid lymphopenia, T cell activation and preferential loss of Th17 subset at the early stage of acute infection. Statistical analysis indicated that CD4 depletion and loss of Th17 cells, rather than Th1 or Treg cells, were correlated with CD4 T cell activation. More importantly, up-regulated IFN-α likely contributed to the functional loss of Th17 cells. Thus, rapidly generalized lymphopenia, preferential loss of Th17 population and T cell activation presented as characteristics of the early immune response in S-OIV-infected patients. These findings, therefore, may be helpful for an earlier diagnosis and further studies of immune pathogenesis of S-OIV infection.

[Difference of immunological and inflammatory indices between mild type and severe type of adult pandemic (H1N1) patients].

OBJECTIVE: To study the difference of immunological and inflammatory indices between mild type and severe type of adult pandemic (H1N1) patients. METHODS: White blood cell, lymphocyte, monocyte, CD4(+) and CD8(+) T lymphocyte counts, level of C3 and C4, CH50, immunoglobulin A/G/M and CRP from 166 pandemic (H1N1) patients during acute and recovery phases were recorded and analyzed. RESULTS: A lowered lymphocyte count and an elevated monocyte count were observed in both groups during acute phase. And both were corrected during recovery phase. The absolute values of CD4(+) and CD8(+) T lymphocytes were much lower in severe group than those in mild group. During acute phase, the level of c-reactive protein (CRP) was elevated in both groups while it was higher in the severe group than that in the mild group. During recovery phase, the CRP level fell after a rise in both groups while it was quicker in the severe group than that in the mild group. During acute phase, the majority of CH50 became mildly elevated. And it was higher in severe patients than mild ones. CONCLUSION: Lymphocyte count, CD4(+) & CD8(+) T lymphocyte counts and CRP & CH50 values provide useful information for the diagnosis of pandemic (H1N1) and the evaluation of its severity.

Surveillance for respiratory infectious diseases caused by 6 common viruses in a recruit training site in the Northern region of China.

BACKGROUND: Recruit training sites are places with a high incidence of respiratory infectious diseases. Effective surveillance for acute respiratory infectious diseases in a recruit training site is an important way to prevent disease outbreaks. METHODS: Eight hundred recruits (722 males and 78 females) enlisted in autumn 2015 received a background survey within 24 h of settlement at the recruit training site, including their general personal information, vaccination history, mental status and clinical symptoms. Then, nasopharyngeal swabs of these recruits were collected to detect common respiratory pathogens [influenza virus type A, influenza virus type B, adenovirus (Adv), human respiratory syncytial virus, human bocavirus and human metapneumovirus] by PCR. In addition, fasting venous blood was collected in the morning for adenovirus IgG antibody detection. During the three months of training, the recruits were monitored for symptoms of respiratory infection, and nasopharyngeal swabs were collected from those with an axillary temperature ≥38 °C and other respiratory symptoms within 4 h of symptom onset. Samples were further examined by PCR. RESULTS: Among the 795 effective nasopharyngeal swab samples collected during survey, two cases of group C type 1 adenovirus were identified by PCR. During the 3 months of training, fever and respiratory symptoms occurred in 39 recruits (incidence rate of 4.9%) and 5 cases of adenovirus were detected (positive rate of 12.8%). Genotyping showed 3 cases of type 4 adenovirus and 2 of type 3 adenovirus. No type 7, 14 or 55 adenovirus was detected. The Adv-IgG positive rate of recruits was 48.2%. Among the 5 Adv positive cases with fever and respiratory symptoms, 4 were Adv-IgG positive. CONCLUSION: The pathogen carrier rate in recruits was low, and only group C adenovirus, which causes mild infection in humans, was detected. No respiratory outbreak was observed at the recruit training site, and sporadic cases were mainly caused by type 3 and type 4 adenoviruses.

A survey of knowledge about hepatitis B among new military recruits in China.

BACKGROUND: Hepatitis B is a disease that affects the liver and is caused by the hepatitis B virus (HBV). Hepatitis B is a serious public health problem in China. The objective of this study was to assess knowledge of and behaviours towards the transmission and prevention of hepatitis B of new military recruits in China. METHODS: A cross-sectional study was conducted among 800 new military recruits. A self-administered, structured questionnaire was used to collect information, and 727 questionnaires were returned completed. Analysis was performed using SPSS 18.0, and P < 0.05 was considered statistically significant. RESULTS: Of the respondents, 665 (91.5%) were male and 62 (8.5%) were female. The mean age was 18.9 ± 1.7 years. A total of 608 respondents (83.6%) demonstrated poor knowledge and 119 (16.4%) adequate knowledge about HBV. Older age, female and higher education level were statistically associated with a higher mean knowledge score. Multivariate logistic regression showed that age (OR = 3.040, 95%CI 1.724-5.359, P < 0.001) and gender (OR = 1.791, 95%CI 1.325-2.421, P < 0.001) were significantly associated with appropriate behavioural practices towards prevention of HBV. CONCLUSION: Against a backdrop of high HBV prevalence in China, new military recruits had poor knowledge of HBV. New recruits need better education about HBV to assist in reducing and preventing HBV infection.

[Analysis of severe acute respiratory syndrome in Beijing].

OBJECTIVE: To study the clinical, laboratory, and radiologic features of 34 cases of severe acute respiratory syndrome (SARS) in Beijing. METHODS: All patients were admitted to the isolation wards. Their demographic, clinical, laboratory, and radiologic characteristics were analyzed. Univariate and multivariate analyses were performed. RESULTS: Eight patients came from a family, and 15 patients were medical staff. The mean age of patients was (33.4 +/- 13.4) years. The latent period varied from 2 to 14 days (median 4 days). The most common symptoms were fever (100%), palpitation (91.7%), myalgia (79.2%), headache (70.8%), diarrhea (73.9%) and cough (58.3%). The mean leucocyte count was (4.6 +/- 1.4) x 10(9)/L, and the mean lymphocyte ratio was 0.27 +/- 0.11. 68.4% of the patients had lymphopenia (absolute lymphocyte count < 1.3 x 10(9)/L). Other common findings included elevated levels of serum alanine aminotransferase, lactate dehydrogenase and erythrocyte sedimentation (76.2%, 28.6% and 47.8%, respectively), and decreased levels of serum iron and albumin (63.2% and 47.8%, respectively). Thirty-two cases had abnormal chest radiographs. In 2 cases in whom typical lung opacities could not be found on the initial plain chest radiographs, thoracic CT proved to be useful. Postmortem examination of 1 patient revealed marked edema with foci of hemorrhage and hyaline membrane formation in the lungs, hemorrhage necrosis and a obvious decline of cells in lymph glands. In a multivariate analysis (Stata 7.0), the independent predictor of an adverse outcome was advanced age (odds ratio per decade of life, 1.6; 95% CI, 1.08 to 2.63; P = 0.007). CONCLUSIONS: Fever, lymphopenia, low serum iron and chest radiograph are helpful to diagnose SARS early; age is the independent predictor of an outcome.

[Characteristics of γδ T cell subsets induced from peripheral blood mononuclear cells of HIV/AIDS patients in vitro].

AIM: To investigate the characteristics of γδ T cell subsets in peripheral blood and Vδ1 and Vδ2 T cell subsets proliferation after induction in vitro, and to provide experimental basis for γδ T cells expansion methods in vitro. METHODS: Percentages of γδ T cells, Vδ1 and Vδ2 T cells in CD3 T cells from 25 cases of HIV/AIDS patients (HIV group) and 31 cases of healthy adults as control (HC group) were investigated with flow cytometry (FCM); and 10 cases peripheral blood mononuclear cells (PBMCs) from each group were induced and cultured for 14 d by using anti-γδ TCR mAb and IL-2, then the cell amounts were counted, γδ T cells and Vδ1, Vδ2 T cells were detected and analyzed with flow cytometry (FCM) at 0 d, 7 d and 14 d. RESULTS: The percentages and absolute counts of γδ T cells and V δ2 T cells in HIV group were significantly lower than those in HC group, but those of Vδ1 subsets were significantly higher than those of HC group. After culture for 14 day, the total cell amount of HC group expanded almost 3 times, but those of HIV group expanded a little; The percentages of γδ T cells in HC group were above 80%, but those in HIV group were only about 35%; the percentages of Vδ2 T cells in HC group were about 65%, but those in HIV group were only about 17%. CONCLUSION: The proportion of γδ T cells in peripheral blood of HIV/AIDS patients decreased significantly, and Vδ1/Vδ2 ratio was inversed; the expansion effect was not so good to use anti-γδ TCR mAb and IL-2 to induce γδ T cells and Vδ2 subsets of HIV/AIDS, and the Vδ1/Vδ2 ratio inversion could not reverse. More efficient culture methods should be explored.

[The comparison between HIV-infected patients' Vdelta2 T cells expansion efficiencies by zoledronic acid and gammadelta TCR monoclonal antibody in vitro].

OBJECTIVE: To find out the more efficient induction method through investigating the expansion efficiencies of HIV-infected patients' Vdelta2 T cells induced by zoledronic acid (Zol) or gammadelta TCR monoclonal antibody (mAb). METHODS: 38 healthy control subjects (HC group) and 65 HIV infected patients (HIV group) were enrolled in this research. Peripheral blood mononuclear cells (PBMCs) of individuals were stimulated by Zol or gammadelta TCR mAb respectively for 14 days at 2.0 x 10(7) cells/ well, and then gammadelta T cells and Vdelta2 subsets frequencies were measured by flow cytometry (FCM) on 0, 7 and 14 day. The absolute numbers of Vdelta2 T cells were calculated and the Vdelta2 T cell expansion efficiencies by these two methods were compared. RESULTS: The absolute numbers and frequencies of Vdelta2 T cell of HIV groups were lower than those of HC groups significantly on 0 day. After 14 days, the frequencies of Vdelta2 T cell of HIV group and HC group were(17.6 +/- 19.8)% and(64.3 +/- 4.5)% respectively, and the expansion indexes of Vdelta2 T cell were 54 +/- 40 and 74 +/- 29 respectively by induction of gammadelta TCR mAb. However, the frequencies of Vgammadelta2 T cell of HIV group and HC group were (69.6 +/- 21.2)% and (97.3 +/- 1.7)% respectively, and the Vgammadelta2 T cell expansion indexes were 538 +/- 11 and 5984 +/- 721 respectively by induction of Zol. CONCLUSION: Zol could induce the vast expansion of Vgammadelta2 T cells of HIV infected patients. The expansion efficiency by Zol was better than that by the gammadelta TCR mAb.

[Changes and analysis of peripheral white blood cells and lymphocyte subsets for patients with pandemic influenza A virus (H1N1) infection].

OBJECTIVE: To investigate the characters and changes of peripheral white blood cells and lymphocyte subsets of patients with pandemic influenza A virus (H1N1) infection and to provide evidences for diagnosis, treatment and prognosis of influenza A (H1N1) infection. METHODS: Peripheral white blood cell parameters and the percentages of lymphocyte subsets in acute and recovery phases of 59 cases of influenza A virus (H1N1) infectious patients (42 mild cases and 17 severe cases) were investigated and analyzed, and compared respectively with those of 43 cases of healthy adults as control (HC) and 24 cases of general influenza A virus (no-H1N1) infectious using whole blood cell analysis and flow cytometry. RESULTS: Peripheral white blood cell counts of mild cases decreased greatly but those of severe cases did not decrease significantly; the neutrophils of severe cases increased significantly in acute phase; similar to general influenza A virus (no-H1N1) infectious, the peripheral lymphocytes, CD3, CD4, CD8 and B cells of all patients with influenza A virus (H1N1) infection decreased greatly in acute phase and quickly recovered in recovery phase; NK and NKT cells absolute counts of severe cases decreased significantly in acute phase, and the decreasing extent of which were more than 20%. CONCLUSION: There were similar characteristics of change in peripheral white blood cells and lymphocyte subsets between patients with pandemic influenza A virus (H1N1) infection and general pandemic A virus (No-H1N1); the great decrease of NK and NKT cells absolute counts may suggest the severe tendency of diseases.

[Changes of blood cells in patients with severe acute respiratory syndrome].

OBJECTIVE: To investigate the changes of blood corpuscles of patients with severe acute respiratory syndrome (SARS) in Beijing. METHODS: Totally 43 patients (21 male and 22 female, 19-74 years old age range) diagnosed as of probable SARS were included in this study. Their corpuscles in the peripheral blood were tested every two days, and the results were analyzed. RESULTS: Patients with SARS were more likely to develop leukocytopenia, lymphopenia and thrombocytopenia in the early period of disease than those in control group. The situation, especially lymphopenia and thrombocytopenia, could not be reversed in patients who died. Persistent low counts of lymphocytes and platelets at presentation might be associated with adverse outcomes. CONCLUSION: Low counts of leukocytes, lymphocytes and platelets were common among patients in the early stage of SARS. Persistent Lymphopenia and thrombocytopenia may be associated with the prognosis.