Differential down-regulation of CD95 or CD95L in chronically HIV-infected cells of monocytic or lymphocytic origin: cellular studies and molecular analysis by quantitative competitive RT-PCR.
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We analysed the expression of CD95/CD95L in two widely used models for studying the cellular effects of chronic infection with human immunodeficiency virus type 1 (HIV-1), i.e. ACH-2 cells, derived from the lymphocytic cell line A301, and U1, derived from monocytic U937 cells. A301 and ACH-2 mounted the same amount of plasma membrane CD95, while U1 had a consistent decrease in CD95 expression. Using different antibodies, we failed to detect the plasma membrane form of its ligand, CD95L, but we could see the intracellular presence of that molecule in A301 cells and, to a lesser extent, in ACH-2 cells, but not in U937 or U1 cells. To confirm the cytofluorimetric data and quantify the expression of CD95L at the RNA level, we developed a quantitative competitive RT-PCR assay. The HUT78 cell line had about 50,000 copies mRNA/1000 cells, three times more after induction with a phorbol ester and ionomycin. ACH-2 expressed about 400- (basal) or 10- (induced) fold less CD95L mRNA than the parental cell line A301; U937 and U1 were below the limit of detection. In cells of lymphoid origin (ACH-2) chronic HIV infection inhibits the expression of CD95L, the phenomenon occurring at the transcriptional level. In cells of monocytic origin (U1) the infection decreases the plasma membrane expression of CD95. This suggests that HIV could trigger different anti-apoptotic strategies which likely depend upon the cell line which is infected. In monocytic cells which act as a viral reservoir, the expression of the molecule whose binding triggers apoptosis decreases, while in lymphoid cells, capable of exerting cytotoxicity, the expression of a molecule which induces apoptosis is reduced. (+info)
Spontaneous and antigen-induced production of HIV-inhibitory beta-chemokines are associated with AIDS-free status.
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The beta-chemokines RANTES, macrophage inflammatory protein (MIP)-1alpha, and MIP-1beta suppress infection by macrophage-tropic strains of HIV and simian immunodeficiency virus (SIV) by binding and down-regulating the viral coreceptor, CCR5. Accordingly, we have examined whether higher levels of CCR5 ligands are associated with a more favorable clinical status in AIDS. A cross-sectional study of 100 subjects enrolled in the Multicenter AIDS Cohort Study at the Baltimore site was conducted to measure chemokine production and lymphocyte proliferation by peripheral blood mononuclear cells (PBMC). Statistical analyses of the data revealed that the production of HIV-suppressive beta-chemokines by HIV antigen-stimulated PBMC was significantly higher in HIV-positive subjects without AIDS compared with subjects with clinical AIDS. Increased chemokine production was also correlated with higher proliferative responses to HIV antigens. Both parameters were significantly lower in the AIDS versus non-AIDS group. Notably, significantly higher levels of MIP-1alpha were also observed with unstimulated PBMC from seronegative subjects at risk for HIV infection released as compared with seropositive and non-Multicenter AIDS Cohort Study seronegative subjects. The association of chemokine production with antigen-induced proliferative responses, more favorable clinical status in HIV infection, as well as with an uninfected status in subjects at risk for infection suggests a positive role for these molecules in controlling the natural course of HIV infection. (+info)
Race-specific HIV-1 disease-modifying effects associated with CCR5 haplotypes.
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Genetic variation in CC chemokine receptor 5 (CCR5), the major HIV-1 coreceptor, has been shown to influence HIV-1 transmission and disease progression. However, it is generally assumed that the same CCR5 genotype (or haplotype) has similar phenotypic effects in different populations. To test this assumption, we used an evolutionary-based classification of CCR5 haplotypes to determine their associated HIV-1 disease-modifying effects in a large well-characterized racially mixed cohort of HIV-1-seropositive individuals. We demonstrate that the spectrum of CCR5 haplotypes associated with disease acceleration or retardation differs between African Americans and Caucasians. Also, we show that there is a strong interactive effect between CCR5 haplotypes with different evolutionary histories. The striking population-specific phenotypic effects associated with CCR5 haplotypes emphasize the importance of understanding the evolutionary context in which disease susceptibility genes are expressed. (+info)
Prevalence of lower genital tract infections among human immunodeficiency virus (HIV)-seropositive and high-risk HIV-seronegative women. HIV Epidemiology Research Study Group.
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This study was undertaken to assess whether the prevalence of lower genital tract infections among human immunodeficiency virus (HIV)-seropositive women was higher than among high-risk HIV-seronegative women at their baseline visit for the HIV Epidemiology Research Study. Results were available for 851 HIV-seropositive and 434 HIV-seronegative women. Human papilloma virus (HPV) infection was more prevalent among HIV-seropositive women (64% vs. 28%). Bacterial vaginosis was common (35% vs. 33%), followed by trichomoniasis (12% vs. 10%), syphilis (8% vs. 6%), Chlamydia trachomatis infection (4% vs. 5%), candidal vaginitis (3% vs. 2%), and Neisseria gonorrhoeae infection (0.8% vs. 0.3%). Alcohol use (odds ratio [OR], 1.8; 95% confidence interval [CI], 1. 3-2.4) and smoking (OR, 1.8; 95% CI, 1.3-2.5) were associated with bacterial vaginosis. Bacterial vaginosis (OR, 2.3; 95% CI, 1.5-3.4), trichomoniasis (OR, 2.3; 95% CI, 1.1-4.7), and syphilis (OR, 3.1; 95% CI, 1.3-7.4) were found to be more prevalent among black women. Our study showed no statistically significant difference in the prevalence of lower genital tract infections except for HPV between HIV-infected and demographically and behaviorally similar HIV-uninfected high-risk women. (+info)
Self-reported bacterial infections among women with or at risk for human immunodeficiency virus infection.
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Bacterial infections are a major cause of morbidity and mortality in persons with human immunodeficiency virus (HIV) infection, particularly women. We performed a cross-sectional analysis of a history of bacterial infections among 1,310 women with or at risk for HIV infection. HIV-seropositive women were significantly more likely than seronegative women to report recent and lifetime histories of bacterial infection, even after history of injection drug use since 1977 was adjusted for; this included recent pneumonia (odds ratio [OR], 3.2; 95% confidence interval [CI], 1.5-6.6), sinusitis (OR, 1.4; 95% CI, 1.0-2.0), and urinary tract infection (OR, 1.5; 95% CI, 1.1-2.1). Compared with HIV-negative women, women with CD4 cell counts of <200 were about eight times more likely to report recent pneumonia (OR, 7.8; 95% CI, 3.4-17.7); those with CD4 cell counts of 200-500 were almost three times more likely to do so (OR, 2.6; CI, 1.2-5.7). Logistic regression analysis revealed that only CD4 cell category and a recent history of smoking had a significant relationship to self-reported pneumonia. (+info)
Regeneration and tolerance factor: a correlate of human immunodeficiency virus-associated T-cell activation.
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Human immunodeficiency virus (HIV) infection causes extensive phenotypic alterations in lymphocytes. Cellular markers that are normally absent or expressed at low levels on quiescent cells are upregulated throughout the disease course. The transmembrane form of regeneration and tolerance factor (RTF) is expressed at negligible levels on resting T cells but is quickly upregulated following in vitro stimulation and activation. Recently, we reported that expression of RTF was significantly higher in cells from HIV-seropositive (HIV(+)) individuals than in cells from HIV-seronegative (HIV(-)) individuals. Because T cells from HIV(+) individuals express markers reflecting chronic activation, we hypothesized that these in vivo-activated cells would coexpress RTF. Flow cytometry was used to assess RTF expression on activated (CD38(+) and HLA-DR(+)) CD4(+) and CD8(+) T cells. HIV(+) individuals had higher percentages of RTF(+) CD38(+) (P < 0.0001) or RTF(+) HLA-DR(+) (P = 0.0001) CD4(+) T cells than HIV(-) individuals. In HIV(+) individuals, increased percentages of CD4(+) T cells that were RTF(+), RTF(+) CD38(+), and RTF(+) HLA-DR(+) correlated inversely with the absolute number and percentage of CD4(+) T cells and correlated positively with plasma beta(2)-microglobulin concentrations. HIV(+) individuals had higher percentages of CD8(+) T cells that were RTF(+) CD38(+) (P = 0.0001) or RTF(+) HLA-DR(+) (P = 0.0010). In HIV(+) individuals, increased percentages of CD8(+) T cells that were RTF(+) HLA-DR(+) correlated inversely with the percentage of CD4(+) T cells, and high percentages of CD8(+) T cells that were RTF(+) CD38(+) correlated positively with plasma beta(2)-microglobulin levels. These findings strongly suggest that increased RTF expression is a correlate of HIV-associated immune system activation. (+info)
The Outpatient Developmental Services Project: integration of pediatric psychology with primary medical care for children infected with HIV.
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OBJECTIVE: To present a model in which pediatric psychology services are programmatically integrated into the primary care of children seen in a special immunology program. The program centers around serial neurodevelopmental/neuropsychological evaluation of children infected with HIV. METHOD: We describe the population served and the particular services provided, with specific focus on how the program was developed. We include a discussion of the barriers to service provision that have been encountered and the strategies employed to overcome these challenges. CONCLUSIONS: This approach, while not ideal, serves as a good example of how pediatric psychology can merge with primary medical care to maximize the benefits of both specialties for a patient population that is underserved in many respects. (+info)
Expression of CD10 by human T cells that undergo apoptosis both in vitro and in vivo.
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This study shows that human postthymic T cells express CD10 when undergoing apoptosis, irrespective of the signal responsible for initiating the apoptotic process. Cells from continuous T-cell lines did not normally express CD10, but became CD10(+) when induced into apoptosis by human immunodeficiency virus (HIV) infection and exposure to CD95 monoclonal antibody, etoposide, or staurosporin. Inhibitors of caspases blocked apoptosis and CD10 expression. Both CD4(+) and CD8(+) T cells purified from normal peripheral blood expressed CD10 on apoptotic induction. CD10 was newly synthesized by the apoptosing cells because its expression was inhibited by exposure to cycloheximide and CD10 mRNA became detectable by reverse transcription-polymerase chain reaction in T cells cultured under conditions favoring apoptosis. To show CD10 on T cells apoptosing in vivo, lymph node and peripheral blood T cells from HIV(+) subjects were used. These suspensions were composed of a substantial, although variable, proportion of apoptosing T cells that consistently expressed CD10. In contrast, CD10(+) as well as spontaneously apoptosing T cells were virtually absent in peripheral blood from normal individuals. Collectively, these observations indicate that CD10 may represent a reliable marker for identifying and isolating apoptosing T cells in vitro and ex vivo and possibly suggest novel functions for surface CD10 in the apoptotic process of lymphoid cells. (+info)