Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 4 of 4

Publication Record

Connections

Cytomegalovirus (CMV) Epitope-Specific CD4 T Cells Are Inflated in HIV CMV Subjects.
Abana CO, Pilkinton MA, Gaudieri S, Chopra A, McDonnell WJ, Wanjalla C, Barnett L, Gangula R, Hager C, Jung DK, Engelhardt BG, Jagasia MH, Klenerman P, Phillips EJ, Koelle DM, Kalams SA, Mallal SA
(2017) J Immunol 199: 3187-3201
MeSH Terms: ADP-ribosyl Cyclase 1, CD4-Positive T-Lymphocytes, Cytomegalovirus, Cytomegalovirus Infections, Epitopes, T-Lymphocyte, Female, HIV Infections, HIV-1, HLA-DR7 Antigen, Humans, Immunologic Memory, Male, Membrane Glycoproteins, Viral Proteins
Show Abstract · Added March 30, 2020
Select CMV epitopes drive life-long CD8 T cell memory inflation, but the extent of CD4 memory inflation is poorly studied. CD4 T cells specific for human CMV (HCMV) are elevated in HIV HCMV subjects. To determine whether HCMV epitope-specific CD4 T cell memory inflation occurs during HIV infection, we used HLA-DR7 (DRB1*07:01) tetramers loaded with the glycoprotein B DYSNTHSTRYV (DYS) epitope to characterize circulating CD4 T cells in coinfected HLA-DR7 long-term nonprogressor HIV subjects with undetectable HCMV plasma viremia. DYS-specific CD4 T cells were inflated among these HIV subjects compared with those from an HIV HCMV HLA-DR7 cohort or with HLA-DR7-restricted CD4 T cells from the HIV-coinfected cohort that were specific for epitopes of HCMV phosphoprotein-65, tetanus toxoid precursor, EBV nuclear Ag 2, or HIV gag protein. Inflated DYS-specific CD4 T cells consisted of effector memory or effector memory-RA subsets with restricted TCRβ usage and nearly monoclonal CDR3 containing novel conserved amino acids. Expression of this near-monoclonal TCR in a Jurkat cell-transfection system validated fine DYS specificity. Inflated cells were polyfunctional, not senescent, and displayed high ex vivo levels of granzyme B, CXCR1, CD38, or HLA-DR but less often coexpressed CD38 and HLA-DR The inflation mechanism did not involve apoptosis suppression, increased proliferation, or HIV gag cross-reactivity. Instead, the findings suggest that intermittent or chronic expression of epitopes, such as DYS, drive inflation of activated CD4 T cells that home to endothelial cells and have the potential to mediate cytotoxicity and vascular disease.
Copyright © 2017 by The American Association of Immunologists, Inc.
0 Communities
1 Members
0 Resources
MeSH Terms
Pyridine Dinucleotides from Molecules to Man.
Fessel JP, Oldham WM
(2018) Antioxid Redox Signal 28: 180-212
MeSH Terms: ADP-ribosyl Cyclase 1, Adenosine Triphosphate, Biosynthetic Pathways, Catalysis, Disease Susceptibility, Energy Metabolism, Homeostasis, Humans, Hydrolysis, Intracellular Space, Male, Mitochondria, NAD, NADP, NADPH Oxidases, Nitric Oxide Synthase, Oxidation-Reduction, Pyridines, Reactive Oxygen Species, Stress, Physiological
Show Abstract · Added March 14, 2018
SIGNIFICANCE - Pyridine dinucleotides, nicotinamide adenine dinucleotide (NAD) and nicotinamide adenine dinucleotide phosphate (NADP), were discovered more than 100 years ago as necessary cofactors for fermentation in yeast extracts. Since that time, these molecules have been recognized as fundamental players in a variety of cellular processes, including energy metabolism, redox homeostasis, cellular signaling, and gene transcription, among many others. Given their critical role as mediators of cellular responses to metabolic perturbations, it is unsurprising that dysregulation of NAD and NADP metabolism has been associated with the pathobiology of many chronic human diseases. Recent Advances: A biochemistry renaissance in biomedical research, with its increasing focus on the metabolic pathobiology of human disease, has reignited interest in pyridine dinucleotides, which has led to new insights into the cell biology of NAD(P) metabolism, including its cellular pharmacokinetics, biosynthesis, subcellular localization, and regulation. This review highlights these advances to illustrate the importance of NAD(P) metabolism in the molecular pathogenesis of disease.
CRITICAL ISSUES - Perturbations of NAD(H) and NADP(H) are a prominent feature of human disease; however, fundamental questions regarding the regulation of the absolute levels of these cofactors and the key determinants of their redox ratios remain. Moreover, an integrated topological model of NAD(P) biology that combines the metabolic and other roles remains elusive.
FUTURE DIRECTIONS - As the complex regulatory network of NAD(P) metabolism becomes illuminated, sophisticated new approaches to manipulating these pathways in specific organs, cells, or organelles will be developed to target the underlying pathogenic mechanisms of disease, opening doors for the next generation of redox-based, metabolism-targeted therapies. Antioxid. Redox Signal. 28, 180-212.
0 Communities
1 Members
0 Resources
20 MeSH Terms
Comment on "The Arabidopsis circadian clock incorporates a cADPR-based feedback loop".
Xu X, Graeff R, Xie Q, Gamble KL, Mori T, Johnson CH
(2009) Science 326: 230; author reply 230
MeSH Terms: ADP-ribosyl Cyclase, Arabidopsis, Calcium, Circadian Rhythm, Cyclic ADP-Ribose, Estradiol, Feedback, Physiological, Niacinamide
Show Abstract · Added February 12, 2015
Dodd et al. (Reports, 14 December 2007, p. 1789) reported that the Arabidopsis circadian clock incorporates the signaling molecule cyclic adenosine diphosphate ribose (cADPR). In contrast, we found that there is no rhythm of cADPR levels nor are there any significant effects on the rhythm by cADPR overexpression, thus raising questions about the conclusions of Dodd et al.
0 Communities
1 Members
0 Resources
8 MeSH Terms
A randomized study of antiviral medication switch at lower- versus higher-switch thresholds: AIDS Clinical Trials Group Study A5115.
Riddler SA, Jiang H, Tenorio A, Huang H, Kuritzkes DR, Acosta EP, Landay A, Bastow B, Haas DW, Tashima KT, Jain MK, Deeks SG, Bartlett JA
(2007) Antivir Ther 12: 531-41
MeSH Terms: ADP-ribosyl Cyclase 1, Adult, Anti-HIV Agents, CD4 Lymphocyte Count, CD8-Positive T-Lymphocytes, Drug Administration Schedule, Drug Resistance, Viral, Drug Therapy, Combination, Female, HIV Infections, HIV-1, Humans, Male, Pilot Projects, RNA, Viral, Reverse Transcriptase Inhibitors, Treatment Outcome, Viremia
Show Abstract · Added March 13, 2015
BACKGROUND - Clinical stability has been observed with continued antiretroviral therapy (ART) in the setting of partial virological suppression. The optimal time to switch treatment in patients with low but detectable HIV-1 RNA is not known.
METHODS - Subjects on stable ART with HIV-1 RNA 200-10,000 copies/ml were randomized to an immediate treatment switch, or to a delayed switch when HIV-1 RNA increased to > or = 10,000 copies/ml or CD4+ T-cell count decreased by 20%. The primary outcome measures were immune activation (proportion of CD8+ T-cells expressing CD38 at week 48) and evolution of genotypic drug resistance.
RESULTS - The study failed to fully accrue the originally planned 108 subjects. Only 47 subjects were randomized to immediate- or delayed-switch arms. Of the subjects in the delayed-switch arm, 10/23 (43%) met the criteria for ART switch during the study (median follow-up 82 weeks). After 48 weeks of observation, the level of immune activation was comparable in the two arms. New resistance mutations were observed in 3/17 and 8/19 subjects in the immediate- and delayed-switch groups, respectively. The loss of future treatment options, however, was comparable in the delayed- and immediate-switch groups.
CONCLUSIONS - Individuals with partial viral suppression tend to remain immunologically stable, however, the accumulation of drug resistance mutations is an ongoing risk. Delayed switch in ART may be a reasonable short-term strategy for individuals with very limited treatment options.
0 Communities
1 Members
0 Resources
18 MeSH Terms