Association of elevated plasma inflammatory biomarker levels with age-related macular degeneration but not cataract in persons with AIDS.

Objective: To evaluate the relationship between plasma biomarkers of systemic inflammation and incident age-related macular degeneration (AMD) in persons with the AIDS.

Design: Case-control study.

Methods: Participants with incident intermediate-stage AMD (N = 26) in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) and controls (N = 60) without AMD.

Shared Mechanisms Govern HIV Transcriptional Suppression in Circulating CD103 and Gut CD4 T Cells.

Latent HIV infection is the main barrier to cure, and most HIV-infected cells reside in the gut, where distinct but unknown mechanisms may promote viral latency. Transforming growth factor β (TGF-β), which induces the expression of CD103 on tissue-resident memory T cells, has been implicated in HIV latency. Using CD103 as a surrogate marker to identify cells that have undergone TGF-β signaling, we compared the HIV RNA/DNA contents and cellular transcriptomes of CD103 and CD103 CD4 T cells from the blood and rectum of HIV-negative (HIV) and antiretroviral therapy (ART)-suppressed HIV-positive (HIV) individuals.

Association of Age-related Macular Degeneration With Mortality in Patients With Acquired Immunodeficiency Syndrome; Role of Systemic Inflammation.

Purpose: To evaluate the relationships among age-related macular degeneration (AMD), mortality, and biomarkers of systemic inflammation in patients with acquired immunodeficiency syndrome (AIDS).

Design: Case-control study.

Methods: In participants with intermediate-stage AMD at enrollment in the Longitudinal Study of the Ocular Complications of AIDS (LSOCA) and 2:1 controls matched for age and sex, cryopreserved baseline plasma specimens were assayed for biomarkers of inflammation, including high-sensitivity C-reactive protein (CRP), interleukin (IL)-6, interferon-γ inducible protein (IP)-10, soluble CD14 (sCD14), soluble CD163 (sCD163), kynurenine/tryptophan (KT) ratio, and intestinal fatty acid binding protein (I-FABP).

A Peptide Mimetic of 5-Acetylneuraminic Acid-Galactose Binds with High Avidity to Siglecs and NKG2D.

We previously identified several peptide sequences that mimicked the terminal sugars of complex glycans. Using plant lectins as analogs of lectin-type cell-surface receptors, a tetravalent form of a peptide with the sequence NPSHPLSG, designated svH1C, bound with high avidity to lectins specific for glycans with terminal 5-acetylneuraminic acid (Neu5Ac)-galactose (Gal)/N-acetylgalactosamine (GalNAc) sequences. In this report, we show by circular dichroism and NMR spectra that svH1C lacks an ordered structure and thus interacts with binding sites from a flexible conformation.

Lymphocyte activation gene-3 expression defines a discrete subset of HIV-specific CD8+ T cells that is associated with lower viral load.

Mechanisms leading to the observed immune dysregulation in chronic HIV infection are not well understood. The MHC-II class ligand, lymphocyte activation gene-3 (LAG-3, CD223), has been implicated in the complex regulation mechanism of immune functions. In this study, we describe a new population of HIV-specific CD8(+) T cells expressing LAG-3.

HIV-specific TGF-beta-positive CD4+ T cells do not express regulatory surface markers and are regulated by CTLA-4.

CD4(+) T cell dysfunction in HIV-1 infection is associated with increased CTLA-4 and TGF-beta expression. In this study we described a population of TGF-beta-positive CD4(+) T cells with multiple HIV specificities. These HIV-specific TGF-beta-positive CD4(+) T cells did not display the immunophenotypic patterns traditionally attributed to regulatory CD4(+) T cells.

TGF-beta and IL-10 production by HIV-specific CD8+ T cells is regulated by CTLA-4 signaling on CD4+ T cells.

Immune dysregulation in HIV-1 infection is associated with increased expression of inhibitory molecules such as CTLA-4, TGF-beta, and IL-10. In this study we examined one potential mechanism for regulating TGF-beta and IL-10 expression by HIV-specific suppressor CD8+ T cells. No overlap between TGF-beta, IL-10, and IFN-gamma cytokine production by HIV-specific CD8+ T cells was observed.

AIDSVAX immunization induces HIV-specific CD8+ T-cell responses in high-risk, HIV-negative volunteers who subsequently acquire HIV infection.

Correlates of immune protection from HIV vaccines remain undefined. The first HIV vaccine efficacy trial in the US and Europe VAX004, was designed to assess whether rgp120 envelope subunits (AIDSVAX B/B, VaxGen) can induce partial or complete protection from HIV-1 infection. No effectiveness in the reduction of either the acquisition of infection or levels of plasma viremia after HIV infection was noted.

Presence of suppressor HIV-specific CD8+ T cells is associated with increased PD-1 expression on effector CD8+ T cells.

Mechanisms leading to the observed immune dysregulation in HIV-1 infection are not well understood. HIV-specific IL-10-positive CD8(+) T cells are increased in advanced HIV disease. We have previously reported that Gag-specific IL-10-positive CD8(+) T cells suppressed cytolysis.

HIV subtypes induce distinct profiles of HIV-specific CD8(+) T cell responses.

CD8(+) T cells play an important role in controlling HIV infection and qualitative differences in HIV-specific CD8(+) responses may determine the degree of immune control. We studied 56 HIV-infected, ARV-naive Ugandans and examined the role of subtypes in modulating their HIV-specific T cell responses. Gag-specific responses were readily detectable in our study population.

Profile of T cell immune responses in HIV-infected children from Uganda.

Human immunodeficiency virus (HIV) immunopathogenesis in children remains poorly understood. We assessed T cell immune activation in antiretroviral therapy-naive children in Uganda (n=154). Increased CD4+ and CD8+ T cell activation strongly correlated with decreased CD4+ T cell percentage.

Pattern of malaria-specific T-cell responses in a cohort of Ugandan children.

Malaria is the leading cause of morbidity and mortality in children in Uganda. The mechanisms whereby malaria parasites are eliminated, or how they may avoid the immune response remain poorly understood. We examined malaria-specific T-cell responses in a well-characterized cohort of African children in an endemic area where malaria transmission occurs throughout the year.

Profile of immunologic recovery in HIV-infected Ugandan adults after antiretroviral therapy.

HIV infection is characterized by a decrease in total CD4 cell count, rising viral load, as well as an increase in immune activation levels. Increased activation can lead to an increase in apoptosis and contribute to CD4 depletion. We evaluated the clinical and immunologic responses of 23 HIV-positive Ugandan volunteers following initiation of antiretroviral therapy (ART).