CD4-Positive T-Lymphocytes ; HIV ; HIV Infections ; virology ; Hepacivirus ; classification ; Hepatitis C ; virology ; Humans ; Liver Transplantation ; Postoperative Period ; Superinfection ; virology

BACKGROUNDThe mechanism of chronic immune activation and impairment of HIV-specific immune responses during chronic infection is not fully understood. However, it is known that high immune activation leads to more rapid progression to AIDS. We hypothesize that CD4(+) T cell-mediated viral antigen presentation contributes to this pathologic immune activation in HIV-infected individuals.

METHODSHIV-specific T cells, responding to noninfectious HIV-1 virions as antigen, were measured by flow cytometric assays. These experimental conditions reflect the in vivo condition where noninfectious HIV-1 represents more than 99% of the antigens.

RESULTSCD4(+) T cells purified from HIV-infected individuals were capable of cross presenting exogenous noninfectious HIV-1 virions to HIV-1-specific CD8(+) T cells. Cross presentation required the entry of HIV-1 to CD4(+) T cells and antigen translocation from endoplasmic reticulum to the Golgi complex. Blocking CD4(+) mediated activation of HIV-specific CD8(+) T cells and redirecting the viral antigens to antigen presenting cells improved HIV-specific T cell responses.

CONCLUSIONSOne possible cause of chronic immune activation and impairment of HIV-1 specific T cell responses is represented by HIV-1 harboring CD4(+) T cells cross presenting HIV-1 antigen to activate CD8(+) T cells. This new mechanism provides the first evidence that cross presentation of noninfectious HIV-1 virions play a role in the immunopathogenesis of HIV-1 infection.

Adult ; Antigen Presentation ; CD4-Positive T-Lymphocytes ; immunology ; virology ; CD8-Positive T-Lymphocytes ; immunology ; HIV-1 ; immunology ; Humans ; Lymphocyte Activation ; Male ; Virion ; immunology

OBJECTIVETo investigate the relationship between coxsackievirus infection and type 1 diabetes mellitus (T1DM), and observe the changes of T lymphocyte subsets in the development of T1DM.

METHODSWe detected Coxsackievirus RNA by reverse transcription PCR, and measured the change in T-lymphocyte subsets by flow cytometry in 22 cases of newly diagnosed T1DM (group I), 30 patients with diabetes for some time (group II), and 30 healthy subjects (group III).

RESULTSThe positivity rate of coxsackie virus RNA in groups I, II, and III was 55.55%, 23.33%, and 6.67%, respectively, showing a significant difference among the 3 groups (P<0.01). Patients with upper respiratory tract infection had a higher positivity rate for coxsackie virus RNA than those without upper respiratory tract infection in group I (P<0.05). Compared with the control group, the percentage of CD3, CD4 and CD4/CD8 ratio decreased significantly in groups I and II (P<0.01 or P<0.05). CD3, CD4 and CD4/CD8 tended to increase in group II in comparison with group I, and there was an significant difference in CD3 and CD4 between the two groups (P<0.01 or P<0.05). Compared with the control group and CVBRNA-negative group, CVBRNA-positive group showed significantly lowered CD3, CD4, CD8 and CD4/CD8 (P<0.01 or P<0.05).

CONCLUSIONThe occurrence and development of type 1 diabetes is closely related to coxsackie virus infection, and the changes in T lymphocyte subsets serves as a probable mechanism of its pathogenicity.

Adolescent ; Adult ; CD4-CD8 Ratio ; CD4-Positive T-Lymphocytes ; immunology ; CD8-Positive T-Lymphocytes ; immunology ; Coxsackievirus Infections ; complications ; immunology ; Diabetes Mellitus, Type 1 ; complications ; virology ; Female ; Humans ; Lymphocyte Count ; Male ; T-Lymphocyte Subsets ; immunology ; Young Adult

OBJECTIVETo study the characteristics of the peripheral blood lymphocyte subsets in pediatric patients with chronic active EBV (CAEBV) infection.

METHODFlow cytometry was used to detect the peripheral blood NK, B, T lymphocyte subsets and the functional, regulatory, naïve, memory and activatory subsets of T lymphocytes in 10 pediatric patients with CAEBV infection, 13 pediatric patients with acute Epstein-Barr virus infection (AEBV) and 12 healthy children in our hospital between March 2004 and April 2008.

RESULTCompared with AEBV group, the number of white blood cells [3325 x 10(6)/L (median, just the same as the following)], lymphocytes (1078 x 10(6)/L), NK cells (68 x 10(6)/L), B cells (84 x 10(6)/L), total T cells (684 x 10(6)/L), CD4+ T cells (406 x 10(6)/L) and CD8+ T cells (295 x 10(6)/L) in CAEBV patients were lower (P<0.05). The functional subset of the CD4+ T cells in CAEBV group (94.5%) was lower than those of the healthy control group (98.7%) (P<0.05), but was still higher than those of AEBV group (74.0%) (P<0.05). While the functional subset of the CD8+ T cells in CAEBV (40.7%) was not dramatically different from the healthy control group (48.3%), but was still higher than that of AEBV group (21.0%) (P<0.05). Although the regulatory subset in CAEBV group (5.0%) was higher than the health control group (4.6%) (P<0.05), but lower than AEBV group (5.8%) (P<0.05). In CAEBV, the proportion of CD4+/CD8+ naïve T cells (32.3%/37.5%) was lower than that of normal group (58.3%/56.6%) (P<0.05), but the proportion of CD4+/CD8+ effective memory T cells in CAEBV group (23.9%/15.1%) was lower than that in AEBV group (36.5%/69.8%) (P<0.05), while the proportion of CD8+ fake naïve T cells in CAEBV (17.5%) was higher than the other 2 groups (P<0.05). The CD8+ activatory subset in CAEBV group (84.4%/34.0%) was higher than that of the healthy control group (44.1%/16.7%) (P<0.05), but still lower than AEBV group (96%/95%) (P<0.05).

CONCLUSIONThere is an imbalance in lymphocyte subsets and disturbance in cellular immunity in CAEBV patients, which may be associated with EBV chronic active infection. Detecting the peripheral haematologic parameters and lymphocyte subsets may be helpful in the diagnosis and the differential diagnosis of CAEBV.

Adolescent ; CD4-CD8 Ratio ; CD4-Positive T-Lymphocytes ; CD8-Positive T-Lymphocytes ; Case-Control Studies ; Child ; Epstein-Barr Virus Infections ; blood ; immunology ; virology ; Female ; Flow Cytometry ; Herpesvirus 4, Human ; Humans ; Killer Cells, Natural ; Lymphocyte Subsets ; immunology ; Male

OBJECTIVETo determine the relative resistance to HIV-1 infection of CD4 + T lymphocytes in HIV-exposed seronegative individuals (ESNs) in China.

METHODSHIV primary isolates were obtained from peripheral whole blood of HIV-infected persons. CD4 + T lymphocytes of Chinese ESNs were separated from peripheral blood mononuclear cells with magnetic cell sorting (MACS). The purified CD4 + T lymphocytes were cocultured with HIV primary isolates. The p24 level was detected and the culture medium was refreshed every 3 days within 2 weeks.

RESULTSFor M tropic HIV strains, p24 level was significantly lower in ESN group than in control group (P < 0.05); for some M tropic HIV strains, even no p24 replicated in ESN group. However, T tropic virus strains had no significant difference between these two groups (P > 0.05).

CONCLUSIONCD4 + T lymphocytes of Chinese ESNs may possess relative resistance to M tropic HIV strains, which may be one of the main influencing factors that result in ESN.

Adult ; CD4-Positive T-Lymphocytes ; immunology ; virology ; China ; Female ; HIV ; classification ; isolation & purification ; pathogenicity ; HIV Infections ; virology ; HIV Seronegativity ; immunology ; Humans ; In Vitro Techniques ; Male ; Sexual Partners

OBJECTIVETo understand the influence of HIV infection on hepatitis C progress in patients co-infected with HIV and hepatitis C virus (HCV) and related immune mechanism.

METHODSTwenty eight patients co-infected with HIV/HCV and 12 patients with simplex HCV infection were enrolled. The liver function and hepatic fibrosis progress were evaluated by detecting peripheral blood and with Fibro-Scan. The viral load of HCV was detected by using real time quantitative PCR. And the percentage of Treg/CD4⁺ T lymphocyte cell was tested by using flow cytometry.

RESULTSThe levels of ALT and ALP in HIV/HCV co-infection group were (76.16 ± 81.248) U/L, (24.507 1 ± 8.194) g/L respectively, higher than those of simplex HCV infection group [(27.475 0 ± 13.985) U/L, (16.966 7 ± 7.189) g/L], the differences were statistical significant. P value was 0.012 and 0.009 respectively. The liver fibrosis index in HIV/HCV co-infection group was 5.950 0-5.825 0 Kpa, higher than that in simplex HIV infection group (5.150 0-1.050 0 Kpa), and the difference was nearly statistical significant (P = 0.077). The HCV viral load in HIV/HCV co-infection group was (6.476 8-5.343 4) lg copy/ml, higher than that in simplex HCV infection group [(1.699 0-2.681 5) lg copy/ml], and the rate of HCV clearance in HIV/HCV co-infection group was 32.14%, lower than that in simplex HCV infection group (75.00%). P value was 0.012 and 0.032 respectively. The percentage of Treg/CD4⁺ T lymphocyte cell in HIV/HCV co-infection group was (7.460 0%-2.287 5%), higher than that in simplex HCV infection group (5.965 0%-2.105 0%), and the difference was significant (P = 0.032). The percentage of Treg/CD4⁺ T lymphocyte cell was significantly related with HCV viral load (ρ = 0.350, P = 0.027), and HCV viral load was significantly related with the liver fibrosis index (ρ = 0.487, P = 0.001).

CONCLUSIONHIV infection could accelerate the progress of hepatitis C, and Treg cells were involved in this progress.

CD4-Positive T-Lymphocytes ; Coinfection ; Disease Progression ; HIV Infections ; complications ; Hepacivirus ; Hepatitis C ; complications ; virology ; Humans ; Liver Cirrhosis ; virology ; Viral Load

Biomarkers ; metabolism ; CD4-Positive T-Lymphocytes ; immunology ; metabolism ; Cytomegalovirus Retinitis ; immunology ; Female ; Humans ; Male ; Polymerase Chain Reaction ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; immunology ; metabolism ; virology

OBJECTIVETo investigate the biological and clinical features of Chinese rhesus monkeys after intravenous (IV) and intrarectal (IR) challenge with SIVmac239 in rhesus monkeys of Chinese origin, and compare the differences between the routes of infection.

METHODSRhesus monkeys of Chinese origin were inoculated with SIVmac239 either by IV (n = 19) or IR (n = 6) routes. Simian immunodeficiency virus (SIV)-specific antibody titer, CD4 + T cell counting, plasma SIV load, lymph node pathology, and clinical manifestations were compared between these two groups 232 or 168 days after challenging.

RESULTSAll SIVmac239-inoculated animals became seropositive for SIV-specific antibodies. SIV-specific IgM was detected in IV groups as from day 10 but was not detected in IR for all the time points. Although SIV-specific IgG was detected as from day 30 in both groups, the IgG titers were ten-fold higher in IV group than in IR group after day 168. CD4 + T-cell counting decreased progressively in IV group but remained stable in IR group over time. Plasma SIV RNA loads peaked in all animals between day 10 and day 14 (10(7) copies/ml), then declined to "setpoint" (10(3) - 10(6) copies/ml) about 2 months later. Most inoculated animals manifested lymphadenopathy. Two animals in IV group and one in IR group died of simian AIDS between day 150 and day 210, as evidenced by the autopsies showing the depletion of lymph tissues, Pneumocystis carinii pneumonia and other opportunity infections. Conclusion IV or IR inoculation of SIVmac239 in Chinese rhesus monkeys will result in chronic SIV infection with a similar clinical feature of natural HIV infection, which provides an excellent experimental animal model for AIDS.

Animals ; CD4-Positive T-Lymphocytes ; metabolism ; China ; Disease Models, Animal ; Female ; Macaca mulatta ; virology ; Male ; Rectum ; virology ; Simian Acquired Immunodeficiency Syndrome ; immunology ; virology ; Simian Immunodeficiency Virus ; immunology ; pathogenicity ; Veins ; virology

BACKGROUNDRheumatic diseases involve multiple organs that are affected by immunological mechanisms. Treatment with corticosteroids and immunosuppressive agents may also increase the frequency of infection. Cytomegalovirus (CMV) is a widespread herpes virus and a well-recognized pathogen, which causes an opportunistic and potentially fatal infection in immunocompromised patients. This retrospective study aimed to investigate the clinical and laboratory characteristics of CMV pneumonia in patients with rheumatic diseases after immunosuppressive therapy in a single center in Shanghai, China.

METHODSEight hundred and thirty-four patients with rheumatic diseases who had undergone CMV-DNA viral load tests were included, and the medical records of 142 patients who were positive for CMV-DNA in plasma samples were evaluated. GraphPad Prism version 5.013 (San Diego, CA, USA) was used to conduct statistical analysis. The correlation between CMV-DNA viral loads and lymphocyte counts was assessed using the Spearman rank correlation coefficient test. Significance between qualitative data was analyzed using Pearson's Chi-squared test. The cut-off thresholds for CMV-DNA viral load and lymphocyte count were determined by receiver operating characteristic (ROC) curve analysis.

RESULTSOne hundred and forty-two patients had positive CMV viral load tests. Of these 142 patients, 73 patients with CMV pneumonia were regarded as symptomatic, and the other 69 were asymptomatic. The symptomatic group received higher doses of prednisolone (PSL) and more frequently immunosuppressants than the asymptomatic group (P < 0.01). The symptomatic group had lower lymphocyte counts, especially CD4+ T-cells, than the asymptomatic group (P < 0.01). By ROC curve analysis, when CD4+ T-cell count was <0.39 × 109/L, patients with rheumatic diseases were at high risk for symptomatic CMV infection. The CMV-DNA load was significantly higher in the symptomatic patients than that in asymptomatic patients (P < 0.01; threshold viral loads: 1.75 × 104 copies/ml). Seven patients had a fatal outcome, and they had lower peripheral lymphocyte counts (P < 0.01), including CD4+ and CD8+ T-cells (P < 0.01).

CONCLUSIONSWhen CD4+ T-cell count is <0.39 × 109/L, patients are at high risk for pulmonary CMV infection. Patients are prone to be symptomatic with CMV-DNA load >1.75 × 104 copies/ml. Lymphopenia (especially CD4+ T-cells), presence of symptoms, and other infections, especially fungal infection, are significant risk factors for poor outcome, and a higher PSL dosage combined with immunosuppressants may predict CMV pneumonia.

CD4-Positive T-Lymphocytes ; metabolism ; China ; Cytomegalovirus ; pathogenicity ; Cytomegalovirus Infections ; genetics ; immunology ; therapy ; virology ; Humans ; Immunosuppression ; methods ; Pneumonia ; genetics ; immunology ; therapy ; virology ; Polymerase Chain Reaction ; Retrospective Studies ; Rheumatic Diseases ; genetics ; immunology ; therapy ; virology ; Viral Load

Acquired Immunodeficiency Syndrome ; epidemiology ; immunology ; virology ; Adolescent ; Adult ; CD4-Positive T-Lymphocytes ; virology ; China ; epidemiology ; Female ; HIV Infections ; epidemiology ; immunology ; virology ; HIV-1 ; Humans ; Male ; Middle Aged ; Viral Load ; Young Adult