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Query: UMLS:C0001175 (AIDS)
 120,706 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The frequency of cytomegalovirus (CMV)-specific CD4+ T lymphocytes was determined in CMV-seropositive rhesus macaques with or without simian immunodeficiency virus (SIV) infection by using the sensitive assays of intracellular cytokine staining and gamma interferon ELISPOT. Both techniques yielded 3- to 1,000-fold-higher frequencies of CMV-specific CD4+ T lymphocytes than traditional proliferative limiting dilution assays. The median frequency of CMV-specific CD4+ T lymphocytes in 23 CMV-seropositive SIV-negative macaques was 0.63% (range, 0.16 to 5.8%). The majority of CMV-specific CD4+ T lymphocytes were CD95(pos) and CD27(lo) but expressed variable levels of CD45RA. A significant reduction (P < 0.05) in the frequency of CMV-specific CD4+ T lymphocytes was observed in pathogenic SIV-infected macaques but not in macaques infected with live attenuated strains of SIV. CMV-specific CD4+ T lymphocytes were not detected in six of nine pathogenic SIV-infected rhesus macaques. CMV DNA was detected in the plasma of four of six of these macaques but in no animal with detectable CMV-specific CD4+ T lymphocytes. In pathogenic SIV-infected macaques, loss of CMV-specific CD4+ T lymphocytes was not predicted by the severity of CD4+ T lymphocytopenia. Neither was it predicted by the pre-SIV infection frequencies of CD45RA(neg) or CCR5(pos) CMV-specific CD4+ T lymphocytes. However, the magnitude of activation, as evidenced by the intensity of CD40L expression on CMV-specific CD4+ T lymphocytes pre-SIV infection, was three- to sevenfold greater in the two macaques that subsequently lost these cells after SIV infection than in the two macaques that retained CMV-specific CD4+ T lymphocytes post-SIV infection. Future longitudinal studies with these techniques will facilitate the study of CMV pathogenesis in AIDS.
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PMID:Decreased frequency of cytomegalovirus (CMV)-specific CD4+ T lymphocytes in simian immunodeficiency virus-infected rhesus macaques: inverse relationship with CMV viremia. 1190 4

Human immunodeficiency virus, type 1 (HIV-1), vpr gene encodes a 14-kDa virion-associated protein, which exhibits significant effects on human cells. One important property of Vpr is its ability to induce apoptosis during infection. Apoptotic induction is likely to play a role in the pathogenesis of AIDS. However, the pathway of apoptosis is not clearly defined. In this report we investigate the mechanism of apoptosis induced by HIV-1 Vpr using a Vpr pseudotype viral infection system or adeno delivery of Vpr in primary human lymphoid cells and T-cells. With either vector, HIV-1 Vpr induced cell cycle arrest at the G(2)/M phase and apoptosis in lymphoid target cells. Furthermore, we observed that with both vectors, caspase 9, but not caspase 8, was activated following infection of human peripheral blood mononuclear cell with either Vpr-positive HIV virions or adeno-delivered Vpr. Activation of the caspase 9 pathway resulted in caspase 3 activation and apoptosis in human primary cells. These effects were coincident with the disruption of the mitochondrial transmembrane potential and induction of cytochrome c release by Vpr. The Vpr-induced signaling pathway did not induce CD95 or CD95L expression. Bcl-2 overexpressing cells succumb to Vpr-induced apoptosis. These studies illustrate that Vpr induces a mitochondria-dependent apoptotic pathway that is distinct from apoptosis driven by the Fas-FasL pathway.
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PMID:HIV-1 Vpr induces apoptosis through caspase 9 in T cells and peripheral blood mononuclear cells. 1209 93

Apoptosis is a morphologically distinct form of cell death involved in many physiological and pathological processes. Expression of the CD95 (APO-1/Fas) ligand (CD95L) is critically involved in activation-induced cell death (AICD) of activated T cells. Here we show that the natural free radical scavenger vitamin E suppresses the activity of the transcription factors NF-kappa B and AP-1, thus blocking expression of CD95L and preventing T cell AICD. Since AICD is a major cause of T cell depletion in AIDS, we examined 35 HIV-1-positive individuals and found that their T cells are more susceptible to AICD than are T cells isolated from healthy controls. Administration of vitamin E suppresses CD95L mRNA expression and protects T cells of HIV-1-infected individuals from CD95-mediated apoptosis. This evidence that vitamin E can affect T cell survival may merit further clinical investigation.
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PMID:Vitamin E inhibits CD95 ligand expression and protects T cells from activation-induced cell death. 1220 69

Apoptotic deletion of expanded B cell populations is essential in avoidance of autoimmune disease and immune regulation of some B cell malignancies. The role of CD4+ T cells in B cell apoptosis is evident from the high incidence of B cell tumors and autoimmunity in patients with T cell diseases such as the acquired immune deficiency syndrome (AIDS). We have previously demonstrated that in Epstein-Barr Virus (EBV) negative Burkitt's lymphoma (BL), a tumor derived from proliferating centroblasts of the germinal center, the malignant lymphocytes can be induced to express Fas (CD95) by ligation of CD40 at the B cell surface. Upon CD40 engagement, BL cells are sensitized to T-cell derived death signals provided by Fas ligand (FasL, CD95L). HBL-3 is a cell line derived from an AIDS-related BL in which the tumor IgM binds the human erythrocyte "i" antigen. To determine whether Fas-mediated apoptosis of BL cells is reduced in the context of antigen to which the tumor IgM binds, we stimulated HBL-3 cells with CD40 ligand (CD40L, CD154) in the presence and absence of human erythrocytes expressing the "i" antigen, and measured Fas-mediated apoptosis upon exposure to an agonistic anti-Fas antibody. We observed that HBL-3 cells were sensitized to Fas-mediated death by exposure to CD40L. When i+ RBCs were present, Fas-mediated apoptosis in HBL-3 cells was reduced by greater than 30%. In contrast, there was no reduction in Fas-mediated apoptosis in the presence of i- (I+) RBCs. These findings demonstrate that Fas-mediated deletion of BL cells is inhibited upon surface IgM engagement by antigen for which the malignant clone has affinity.
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PMID:Inhibition of Fas-mediated apoptosis by antigen: implications for lymphomagenesis. 1248 98

Infection by human immunodeficiency virus (HIV) causes persistent chronic inflammation. Viral Tat protein plays a role in the intracellular increase of reactive oxygen species (ROS) thus increasing apoptotic index, mostly the one mediated by FAS/CD95, and depleting CD4+ T lymphocytes. The aim of this study was to investigate whether there is a relationship between an extensive array of redox status indices (glutathione (GSH), malondialdehyde (MDA), peroxidation potential, total antioxidant status, glutathione peroxidase (GPx), superoxide dismutase (SOD), total hydroperoxide (TH), DNA fragmentation) and relative CD4, CD95, CD38/CD8 T lymphocyte counts in HIV/AIDS patients compared to healthy subjects. Blood samples from 85 HIV/AIDS patients and 40 healthy subjects were tested by spectrophotometric techniques in order to measure oxidative stress indices, and by flow cytometry to quantify T cell subsets. Patients were divided in two groups according to CDC 1993 guidelines. CD95 and CD38 increase paralleled the severity of HIV infection. Both a reduction of GSH levels and an increase in MDA and TH levels were detected in the plasma of HIV+ patients. These patients also showed an increase of DNA fragmentation in lymphocytes as well as a significant (P<0.05) reduction of GPx and an increase in SOD activity in erythrocytes. Relatively to the control group, HIV-infected patients had significantly differences in global indices of total antioxidant status. These results corroborate that substantial oxidative stress occurs during HIV infection. To our knowledge this study is the first relating oxidative stress indices with both CD38/CD8 and CD95 lymphocytes subsets.
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PMID:Contribution to characterization of oxidative stress in HIV/AIDS patients. 1259 Oct 17

Today, the most adequate and complete explanation of the main phenomena of clinico-immunological disease picture was suggested by D. Ho and his team (1998). According to their model, HIV infection is not slow infection, but acute productive process, lasting for many years with development AIDS. First of all, in this process specific cytotoxic lymphocytes and antibody-dependent cell cytotoxicity play an active role, as well as apoptotic processes, hyperproduction of pro-inflammatory cytokines, development of autoimmune disorders, direct cytotoxic action of envelope viral proteins The investigations, carried out in Scientific Educational and Industrial Complex "Clinical Immunology" of Rostov-Don State Medical University, have shown that the changes of macrophage functional activity during HIV infection are in dependence upon many factors, especially patient's age. The progression of HIV infection is accompanied with increase of CD95 expression on all lymphocytes, but especially on CD4(+) subpopulation at the stage of AIDS-associated infections. In this group of lymphocytes there is the highest number of cells with DNA degradation that is characteristic of terminal phase of apoptosis. It is possible to make a conclusion that both the viral factors, and the functional features of patient's immune system have great importance for pathogenesis of one or another variant of HIV infection course.
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PMID:HIV Infection: Progress and Problems. 1268 41

Death-associated protein kinase (DAP kinase) is a proapoptotic serine/threonine kinase that has been shown to play a role in both death-receptor signaling and mitochondrial signaling pathways of apoptosis. DAP kinase activates the p19ARF-p53 apoptotic checkpoint. In this study we report that the expression of DAP kinase, p19ARF, p53, and p21WAF1 was significantly down-regulated in the chronically HIV-1SF2-infected HUT78 T cells (HUT78/HIV-1SF2) as compared to uninfected HUT78 cells. An increased proportion of HUT78/HIV1SF2 cells was detected in S phase and a decreased proportion in G0/G1 phase indicating that more HUT78/HIV1SF2 cells progressed through the G1/S transition. Furthermore, HUT78/HIV-1SF2 cells showed increased resistance to CD95-mediated apoptosis as compared to HIV-1SF2-uninfected HUT78 cells and activation of caspase-3, -8, and -9 was significantly reduced in HUT78/HIV-1SF2 cells. These data suggest that down-regulation of DAP kinase and downstream signaling factors may be one of the mechanism that HIV-1 may employ to protect the infected host cells from cell death and to allow persistent HIV-1 replication.
AIDS Res Hum Retroviruses 2004 Feb
PMID:Chronic HIV type 1 infection down-regulates expression of DAP kinase and p19ARF-p53 checkpoint and is associated with resistance to CD95-mediated apoptosis in HUT78 T cells. 1501 6

To investigate HIV-1-related B cell disorders, the quantity of CD27 positive (CD27+) B cells and their CD38, CD95, and bcl-2 intensities were examined by flow cytometry analysis in 16 drug-naive patients, 27 highly active antiretroviral therapy (HAART)-treated patients, and 20 uninfected controls. CD27+ B cells have been recognized as memory B cells. The mean percentage of CD27+ B cells was significantly lower in drug-naive patients (11.9%) and in HAART-treated patients (16.1%) than in controls (31.4%) (p < 0.01). The intensities of CD38 and CD95 on CD27+ B cells were higher in drug-naive patients than in controls (p < 0.01 in CD95). The intensity of CD95 on CD27+ B cells in HAART-treated patients was lower than that of drug-naive patients, but significantly higher than that of controls (p < 0.01). The intensity of bcl-2 on CD27+ B cells was equivalent among the three groups. These findings suggest that disturbance of peripheral B cell composition, exemplified by CD27+ B cell reduction, exists in both drug-naive and HAART-treated HIV-1-infected patients. In addition, the augmented apoptotic state of CD27+ B cells found in HAART-treated patients with undetectable viral loads, indicated by CD95 elevation, suggests that some HIV-1-related B cell disorders last for years after effective antiviral therapy.
AIDS Res Hum Retroviruses 2004 Feb
PMID:Selective CD27+ (memory) B cell reduction and characteristic B cell alteration in drug-naive and HAART-treated HIV type 1-infected patients. 1501 10

To investigate HIV-1-related B cell disorders, the quantity of peripheral CD27 negative (CD27-) B cells, their CD38, CD95, and bcl-2 intensities, and their apoptosis susceptibility were examined by flow cytometry analysis in 16 drug-naive patients, 27 HAART-treated patients, and 20 uninfected controls. CD27- B cells have been recognized as naive B cells. The mean percentage of CD27- B cells was significantly higher in drugnaive patients (88.1%) and in HAART-treated patients (83.9%) than in controls (68.6%) (p < 0.01). The intensities of CD38 and CD95 on CD27- B cells were significantly higher in drug-naive patients than in controls (p < 0.01). The intensity of CD95 on CD27- B cells in HAART-treated patients was lower than that of drug-naive patients, but significantly higher than that of controls (p < 0.01). The intensity of bcl-2 on CD27- B cells in drug-naive patients was lower than that of controls. In drug-naive patients, CD27-B cells with high CD38 expression represented low bcl-2 expression. The CD27- B cells of drug-naive patients showed an increased susceptibility to apoptosis, characterized by diminished cell size and a high frequency of annexin-V binding, compared with controls and HAART-treated patients. These findings suggested that HIV-1 infection affects peripheral CD27- (naive) B cells as well as CD27+ (memory) B cells and that CD27- B cells might be activated and rendered highly susceptible to apoptosis by HIV-1 infection. Some phenotypic alterations in CD27- B cells may continue after the reduction of HIV-1 loads by effective antiviral therapy.
AIDS Res Hum Retroviruses 2004 Jun
PMID:Increased frequency of CD27- (naive) B cells and their phenotypic alteration in HIV type 1-infected patients. 1524 38

Termination of an immune response requires elimination of activated T lymphocytes by activation-induced cell death (AICD). In AICD, CD95 (Apo-1/Fas) ligand (L) triggers apoptosis of CD95-positive activated T lymphocytes. In AIDS patients, AICD is strongly enhanced and accelerated. We and others have previously shown that HIV-1 trans-activator of transcription (HIV-1 Tat) sensitizes T cells toward CD95-mediated apoptosis and up-regulates CD95L expression by affecting the cellular redox balance. In this study, we show that it is hydrogen peroxide (H(2)O(2)) that functions as an essential second messenger in TCR signaling. The H(2)O(2) signal combined with simultaneous calcium (Ca(2+)) influx into the cytosol constitutes the minimal requirement for induction of CD95L expression. Either signal alone is insufficient. We further show that HIV-1 Tat interferes with TCR signaling and induces a H(2)O(2) signal. H(2)O(2) generated by HIV-1 Tat combines with CD4-dependent calcium influx and causes massive T cell apoptosis. Thus, our data provide an explanation for CD4(+) T lymphocyte depletion during progression of AIDS.
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PMID:HIV-1 trans-activator of transcription substitutes for oxidative signaling in activation-induced T cell death. 1584 21


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