In Vitro Cell-Mediated Immune Responses of Human Immunodeficiency Virus-Infected and -Uninfected Individuals to Whole Cytomegalovirus Antigens and Their Subunits

Weinberg, Adriana; Spritzler, John; Nokta, Mostafa; Schrier, Rachel; Landay, Alan; Brown, Darby; Pollard, Richard B.

doi:10.1128/cvi.00479-07

Cited by 7 publications

(5 citation statements)

References 39 publications

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“…Lymphocyte proliferation assays (LPA) were performed at the designated PACTG core immunology laboratories using overnight shipped blood as previously described [ 13 ]. The laboratories used the same lot of CMV cell lysate and mock-infected control antigens prepared in Dr. Weinberg’s laboratory as previously described [ 14 ] and a consensus inter-AIDS networks LPA protocol [ 15 ]. Stimulation indices ≥3 defined response.…”

Section: Methodsmentioning

confidence: 99%

Effect of Cytomegalovirus Co-Infection on Normalization of Selected T-Cell Subsets in Children with Perinatally Acquired HIV Infection Treated with Combination Antiretroviral Therapy

et al. 2015

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BackgroundWe examined the effect of cytomegalovirus (CMV) co-infection and viremia on reconstitution of selected CD4+ and CD8+ T-cell subsets in perinatally HIV-infected (PHIV+) children ≥ 1-year old who participated in a partially randomized, open-label, 96-week combination antiretroviral therapy (cART)-algorithm study.MethodsParticipants were categorized as CMV-naïve, CMV-positive (CMV+) viremic, and CMV+ aviremic, based on blood, urine, or throat culture, CMV IgG and DNA polymerase chain reaction measured at baseline. At weeks 0, 12, 20 and 40, T-cell subsets including naïve (CD62L+CD45RA+; CD95-CD28+), activated (CD38+HLA-DR+) and terminally differentiated (CD62L-CD45RA+; CD95+CD28-) CD4+ and CD8+ T-cells were measured by flow cytometry.ResultsOf the 107 participants included in the analysis, 14% were CMV+ viremic; 49% CMV+ aviremic; 37% CMV-naïve. In longitudinal adjusted models, compared with CMV+ status, baseline CMV-naïve status was significantly associated with faster recovery of CD8+CD62L+CD45RA+% and CD8+CD95-CD28+% and faster decrease of CD8+CD95+CD28-%, independent of HIV VL response to treatment, cART regimen and baseline CD4%. Surprisingly, CMV status did not have a significant impact on longitudinal trends in CD8+CD38+HLA-DR+%. CMV status did not have a significant impact on any CD4+ T-cell subsets.ConclusionsIn this cohort of PHIV+ children, the normalization of naïve and terminally differentiated CD8+ T-cell subsets in response to cART was detrimentally affected by the presence of CMV co-infection. These findings may have implications for adjunctive treatment strategies targeting CMV co-infection in PHIV+ children, especially those that are now adults or reaching young adulthood and may have accelerated immunologic aging, increased opportunistic infections and aging diseases of the immune system.

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Section: Methodsmentioning

confidence: 99%

Effect of Cytomegalovirus Co-Infection on Normalization of Selected T-Cell Subsets in Children with Perinatally Acquired HIV Infection Treated with Combination Antiretroviral Therapy

et al. 2015

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“…Lymphocyte proliferation was assessed by [methyl- 3 H]thymidine incorporation using four replicate wells as previously described 9 using the following antigens: Candida albicans (20 µg/mL, Greer Laboratories, Lenoir, NC), tetanus toxoid, (0.5 Lfu/mL, Connaught Laboratories, Willowdale, Ontario), HIV-1 p24 or control antigen (1 µg/ml, Protein Sciences, Meriden, CT), HIV-1 env2–3 SF2 or control antigen, (0.5 µg/ml, Chiron Corporation, Emeryville, CA), Mycobacterium avium complex (MAC) antigen (0.5 µg/mL Statens Seruminstitut, Copenhagen, Denmark), cytomegalovirus or control antigen (1/50 dilution, provided by Dr. Adriana Weinberg, University of Colorado Denver) 10 , and alloantigens consisting of pooled PBMC from 15 unrelated donors that had been previously gamma-irradiated, cryopreserved, and stored in liquid nitrogen. PHA (5 µg/mL, Sigma, St.…”

Section: Methodsmentioning

confidence: 99%

Augmented HIV-Specific Interferon-Gamma Responses, But Impaired Lymphoproliferation During Interruption of Antiretroviral Treatment Initiated in Primary HIV Infection

Connick

Bosch²,

Aga³

et al. 2011

JAIDS Journal of Acquired Immune Deficiency Syndromes

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Background Antiretroviral therapy (ART) introduced during primary HIV infection followed by treatment interruption (TI) is postulated to enhance virologic control through induction of HIV-specific CD4+ T-cells, which foster virus-specific CD8+ T-cells that suppress virus replication. This hypothesis was evaluated in 21 subjects enrolled in ACTG 709, a substudy of ACTG 371, which prospectively evaluated subjects who received ≥1 year of ART initiated in acute or recent HIV infection followed by TI. Methods Lymphoproliferation was assessed by [methyl-3H]thymidine incorporation and HIV-specific CD8+ T-cell interferon-gamma responses by enzyme-linked immunospot-forming (ELISPOT) assays. Virologic success was defined as sustained viral load <5,000 copies/mL for 24 weeks after TI. Results HIV-specific lymphoproliferative responses were detected at least once in 5 (24%) of 21 subjects, were generally transient, and were unrelated to HIV-specific interferon-gamma responses (p>0.4). HIV-specific CD8+ interferon-gamma responses increased after 48 weeks of ART (p=0.03), but failed to predict virologic success (p=0.18). Compared to seronegative subjects, lymphoproliferation to Candida, cytomegalovirus, and alloantigens was similar in HIV-infected subjects during ART, but lower during TI (p≤0.04). Conclusion HIV-specific CD8+ T-cell interferon-gamma responses expand during ART following primary HIV infection, but are not related to HIV-specific lymphoproliferative responses nor virologic success. Impaired non-HIV antigen-specific lymphoproliferation associated with TI suggests this strategy could be deleterious.

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“…CMV is well known to induce high levels of multiple cytokines ( particularly IFN-γ) [64], which seem to be much higher and broader than that induced by HIV in vitro (Dr Rachel Schrier, unpublished observation). Blood plasma levels of IFN-γ-inducible protein 10, TNF-RII, and D-dimer are higher in people coinfected with CMV and HIV as compared to those in HIV-monoinfected subjects, suggesting that CMV might specifically drive expression of these biomarkers [65].…”

Section: Hiv Versus CMVmentioning

confidence: 99%

Cytomegalovirus and HIV: A Dangerous Pas de Deux

2016

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Human immunodeficiency virus (HIV)-infected adults who take stable antiretroviral therapy (ART) are at risk for early onset of agerelated diseases. This is likely due to a complex interaction between traditional risk factors, HIV infection itself, and other factors, such as underlying immune dysfunction and persistent inflammation. HIV disrupts the balance between the host and coinfecting microbes, worsening control of these potential pathogens. For example, HIV-infected adults are more likely than the general population to have subclinical bursts of cytomegalovirus (CMV) replication at mucosal sites. Production of antigens can activate the immune system and stimulate HIV replication, and it could contribute to the pathogenesis of adverse outcomes of aging, like cardiovascular disease and neurocognitive impairment. Further investigation of the relationships between CMV, immune dysfunction, and unsuccessful aging during chronic HIV infection is warranted.

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In Vitro Cell-Mediated Immune Responses of Human Immunodeficiency Virus-Infected and -Uninfected Individuals to Whole Cytomegalovirus Antigens and Their Subunits

Abstract: The aim of this study was to optimize the ability to detect cytomegalovirus (CMV)-specfic cell-mediated immunity (

Cited by 7 publications

References 39 publications

Effect of Cytomegalovirus Co-Infection on Normalization of Selected T-Cell Subsets in Children with Perinatally Acquired HIV Infection Treated with Combination Antiretroviral Therapy

Effect of Cytomegalovirus Co-Infection on Normalization of Selected T-Cell Subsets in Children with Perinatally Acquired HIV Infection Treated with Combination Antiretroviral Therapy

Augmented HIV-Specific Interferon-Gamma Responses, But Impaired Lymphoproliferation During Interruption of Antiretroviral Treatment Initiated in Primary HIV Infection

Cytomegalovirus and HIV: A Dangerous Pas de Deux

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