Alan Landay

Rush University Medical Center, Chicago, Illinois, United States

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Publications (344)1957.93 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: All-cause mortality and serious non-AIDS events (SNAEs) in individuals with HIV-1 infection receiving antiretroviral therapy are associated with increased production of interleukin-6 which appears to be driven by monocyte/macrophage activation. Plasma levels of other cytokines or chemokines associated with immune activation might also be biomarkers of an increased risk of mortality and/or SNAEs. Baseline plasma samples from 142 participants enrolled into the Strategies for Management of Antiretroviral Therapy study, who subsequently died, and 284 matched controls, were assayed for levels of 15 cytokines and chemokines. Cytokine and chemokine levels were analysed individually and when grouped according to function (innate/proinflammatory response, cell trafficking and cell activation/proliferation) for their association with the risk of subsequent death. Higher plasma levels of proinflammatory cytokines (interleukin-6 and tumour necrosis factor-α) were associated with an increased risk of all-cause mortality but in analyses adjusted for potential confounders, only the association with interleukin-6 persisted. Increased plasma levels of the chemokine CXCL8 were also associated with all-cause mortality independently of hepatitis C virus status but not when analyses were adjusted for all confounders. In contrast, higher plasma levels of cytokines mediating cell activation/proliferation were not associated with a higher mortality risk and exhibited a weak protective effect when analysed as a group. Whereas plasma levels of interleukin-6 are the most informative biomarker of cytokine dysregulation associated with all-cause mortality in individuals with HIV-1 infection, assessment of plasma levels of CXCL8 might provide information about causes of mortality and possibly SNAEs.
    AIDS (London, England) 02/2015; · 6.56 Impact Factor
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    ABSTRACT: Chronic inflammation and immune activation occur in both HIV infection and normal ageing and are associated with inflammatory disease. However, the degree to which HIV influences age-related innate immune changes, and the biomarkers which best reflect them, remains unclear. We measured established innate immune ageing biomarkers in 309 individuals including 88 virologically-suppressed (VS) and 52 viremic (viral load ≤ and >50 copies/ml respectively) HIV+ individuals. Levels of soluble (ie. CXCL10, soluble CD163, neopterin) and cellular (ie. proportions of inflammatory CD16+ monocytes) biomarkers of monocyte activation were increased in HIV+ individuals and were only partially ameliorated by viral suppression. Viremic and VS HIV+ individuals show levels of age-related monocyte activation biomarkers that are similar to uninfected controls aged 12 and 4 years older respectively. Viremic HIV infection was associated with an accelerated rate of change of some monocyte activation markers (eg. neopterin) with age, whilst in VS individuals, subsequent age-related changes occurred at a similar rate as in controls, albeit at a higher absolute level. We further identified CXCL10 as a robust soluble biomarker of monocyte activation, highlighting the potential utility of this chemokine as a prognostic marker. These findings may partially explain the increased prevalence of inflammatory, age-related diseases in HIV+ individuals and potentially indicate the pathological mechanisms underlying these diseases which persist despite viral suppression.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 02/2015; · 4.39 Impact Factor
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    ABSTRACT: With the advent of antiretroviral therapy that can control virus replication below the detection levels of conventional assays, a new clinical landscape of AIDS emerged, in which non-AIDS complications prevail over AIDS-defining conditions. These comorbidities are diverse and affect multiple organs, thus resulting in cardiovascular, kidney, neurocognitive and liver disease, osteopenia/osteoporosis, and cancers. A common feature of these conditions is that they are generally associated with accelerated aging. The mechanism behind these comorbidities is chronic excessive inflammation induced by HIV infection, which persists under antiretroviral therapy. Progressive simian immunodeficiency virus (SIV) infection of nonhuman primates (NHPs) closely reproduces these comorbidities and offers a simplified system in which most of the traditional human risk factors for comorbidities (i.e., smoking, hyperlipidemia) are absent. Additionally, experimental conditions can be properly controlled during a shorter course of disease for SIV infection. As such, NHPs can be employed to characterize new paradigms of AIDS pathogenesis and to test the efficacy of interventions aimed at alleviating non-AIDS-related comorbidities.
    Current HIV/AIDS Reports 01/2015;
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    ABSTRACT: Despite the use of HAART to control HIV, systemic immune activation and inflammation persists with the consequence of developing serious non-AIDS events. The mechanisms that contribute to persistent systemic immune activation have not been well defined. The intestine is the major source of "sterile" inflammation and plays a critical role in immune function; thus, we sought to determine whether intestinal gene expression was altered in virally controlled HIV+ individuals. Gene expression was compared in biopsy samples collected from HIV- and HIV+ individuals from the ileum, right colon (ascending colon), and left colon (sigmoid). Affymetrix gene arrays were performed on tissues and pathway analyses were conducted. Gene expression was correlated with systemic markers of intestinal barrier dysfunction and inflammation and intestinal microbiota composition. Genes involved in cellular immune response, cytokine signaling, pathogen-influenced signaling, humoral immune response, apoptosis, intracellular and second messenger signaling, cancer, organismal growth and development, and proliferation and development were upregulated in the intestine of HIV+ individuals with differences observed in the ileum, right, and left colon. Gene expression in the ileum primarily correlated with systemic markers of inflammation (e.g., IL7R, IL2, and TLR2 with serum TNF) whereas expression in the colon correlated with the microbiota community (e.g., IFNG, IL1B, and CD3G with Bacteroides). These data demonstrate persistent, proinflammatory changes in the intestinal mucosa of virally suppressed HIV+ individuals. These changes in intestinal gene expression may be the consequence of or contribute to barrier dysfunction and intestinal dysbiosis observed in HIV.
    AIDS (London, England) 01/2015; · 6.56 Impact Factor
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    ABSTRACT: Interleukin-8 (IL-8, CXCL8) plays important roles in immune responses at mucosal sites including in the lower genital tract. Since several types of bacteria produce proteases that cleave IL-8 and many types of bacteria can be present in lower genital tract microbiota, we assessed genital fluids for IL-8 cleavage/alteration. Genital fluids collected by lavage from 200 women (23 HIV-seronegative and 177 HIV-seropositive) were tested for IL-8 cleavage/alteration by ELISA. IL-8 cleaving/altering activity was observed in fluids from both HIV-positive (28%) and HIV-negative women (35%). There was no clear relationship between the activity and the types of bacteria present in the lower genital tract as determined by high-throughput sequencing of the 16S rRNA gene. Protease inhibitors specific for matrix metalloproteinases (MMPs) reduced the activity and a multiplex assay that detects both inactive and active MMPs showed the presence of multiple MMPs, including MMP-1, -3, -7, -8, -9, -10 and -12 in genital secretions from many of the women. The IL-8-cleaving/altering activity significantly correlated with active MMP-9 as well as with cleavage of a substrate that is acted on by several active MMPs. These studies show that multiple MMPs are present in the genital tract of women and strongly suggest that MMP-9 in genital secretions can cleave IL-8 at this mucosal site. These studies suggest that MMP-mediated cleavage of IL-8 can modulate inflammatory responses in the lower genital tract.
    PLoS ONE 01/2015; 10(1):e0116911. · 3.53 Impact Factor
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    ABSTRACT: Previous studies have suggested that glycogen expression in the vaginal epithelium decreases during menopause, resulting in reduced levels of lactobacilli. However, free glycogen in genital fluids and its relationship with Lactobacillus levels have not been compared in premenopausal and postmenopausal women. Eighty-two cervicovaginal lavage samples were collected at different phases of the menstrual cycle from 11 premenopausal (4 HIV-uninfected and 7 HIV-infected) and 12 postmenopausal (7 HIV-uninfected and 5 HIV-infected) women during a 1- to 3-month period. Free glycogen was quantified in genital fluids. Lactobacillus levels were quantified by real-time polymerase chain reaction. Estrogen and progesterone levels in blood were determined by enzyme-linked immunosorbent assay. Free glycogen was detected in both premenopausal and postmenopausal women. Across all samples, those from postmenopausal women had significantly lower levels of free glycogen than those from premenopausal women (median, 0.002 vs 0.065 μg/μL, respectively; P = 0.03). Lactobacillus levels correlated positively with free glycogen in both premenopausal (Spearman r = 0.68, P < 0.0001) and postmenopausal (r = 0.60, P < 0.002) women. Samples from premenopausal women had higher Lactobacillus levels and lower vaginal pH (median log, 8.1; median pH, 4) than those from postmenopausal women (median log, 7.1; median pH, 4.6), although these differences were not significant. HIV status had no significant effect on these relationships. Free glycogen is detected in both premenopausal and postmenopausal women and correlates with Lactobacillus in both groups. These results point to the complexity of the relationship between menopause and vaginal microbiota and indicate that more careful studies of the role of glycogen are warranted.
    Menopause (New York, N.Y.) 12/2014; · 3.08 Impact Factor
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    ABSTRACT: Abstract Investigations into apoptotic pathways, intrinsic and extrinsic, and the effects of highly active antiretroviral therapy (HAART) on T cell death via those pathways may provide insight into the mechanisms of and barriers to immune recovery. HIV-1-infected patients were enrolled into a randomized, controlled study of the immune effects of a lopinavir/ritonavir (LPV/r)-based versus an efavirenz (EFV)-based HAART regimen in antiretroviral-naive subjects with CD4(+) counts <350 cells/mm(3). Patients were randomized to receive TDF/FTC/EFZ or TDF/FTC plus LPV/r. Fourteen patients were enrolled and 10 patients completed 6 months of therapy as per the protocol. CD4(+) counts were measured before and during HAART therapy. We isolated T cell subsets to measure ex vivo apoptosis by propidium iodide staining. We also assessed caspase activation for the intrinsic and extrinsic pathways of apoptosis, as well as effector caspase activation. We also measured mitochondrial membrane potential. Cells were analyzed by flow cytometry. All patients had increased activation of caspase 8 (extrinsic pathway), caspase 9 (intrinsic pathway), effector caspases 3/7, and low mitochondrial membrane potential at baseline compared to controls. By 4 weeks, there was a decrease in activation of all caspases, but little further decrease by week 24. T cell mitochondrial membrane potential did not increase until week 12, but continued to increase until week 24. The only predictor of CD4(+) count increase was the increase in mitochondrial membrane potential of naive cells at 6 months (r=0.66, p=0.038). This suggests that positive selection of naive CD4(+) T cells in the thymus is the major determinant of CD4(+) recovery.
    AIDS Research and Human Retroviruses 11/2014; · 2.46 Impact Factor
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    ABSTRACT: Monocyte activation during HIV-1 infection is associated with increased plasma levels of inflammatory markers and increased risk for premature development of age-related diseases. Because activated monocytes primarily use glucose to support cellular metabolism, we hypothesized that chronic monocyte activation during HIV-1 infection induces a hypermetabolic response with increased glucose uptake. To test this hypothesis, we evaluated glucose transporter 1 (Glut1) expression and glucose uptake by monocyte subpopulations in HIV-seropositive (HIV(+)) treatment-naive individuals (n = 17), HIV(+) individuals on combination antiretroviral therapy with viral loads below detection (n = 11), and HIV-seronegative (HIV(-)) individuals (n = 16). Surface expression of Glut1 and cellular uptake of the fluorescent glucose analog 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose were analyzed by flow cytometry on monocyte subpopulations. Irrespective of treatment status, monocytes from HIV(+) persons had significantly increased surface expression of Glut1 compared with those from HIV(-) controls. Nonclassical (CD14(+)CD16(++)) and intermediate (CD14(++)CD16(+)) monocyte subpopulations showed higher Glut1 expression than did classical (CD14(++)CD16(-)) monocytes. Intermediate monocytes from treatment-naive HIV(+) individuals also showed increased uptake of 2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl) amino)-2 deoxyglucose compared with those from HIV(-) controls. Our results show that HIV infection is associated with increased glucose metabolism in monocytes and that Glut1 expression by proinflammatory monocytes is a potential marker of inflammation in HIV-infected subjects. However, the possibility exists whereby other Gluts such as Glut3 and Glut4 may also support the influx of glucose into activated and inflammatory monocyte populations.
    Journal of immunology (Baltimore, Md. : 1950). 11/2014;
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    ABSTRACT: Hepatitis C virus (HCV) viremia is thought to have broad systemic effects on the cellular immune system that go beyond its impact on just those T cells that are HCV specific. However, previous studies of chronic HCV and circulating T-cell subsets (activation and differentiation phenotypes) in HIV negatives used general population controls, rather than a risk-appropriate comparison group. Studies in HIV positives did not address overall immune status (total CD4 count).
    JAIDS Journal of Acquired Immune Deficiency Syndromes 11/2014; 67(3):295-303. · 4.39 Impact Factor
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    ABSTRACT: HIV IRs and INRs show increased galectin-9 expression on NK and CD4+ T cells.•INRs have less CD16+CD56+ and CD16+CD56− NK cells that express TIM-3 than HIV IRs.•The frequency of TIM-3+CD4+ cells in PBMC is reduced in INRs compared to HIV IRs.•TIM-3 expression on NK and T cells correlates with peripheral CD4 count.
    Clinical Immunology 10/2014; · 3.99 Impact Factor
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    ABSTRACT: Alterations in the gut microbiota composition are associated with food allergy. Toll-like receptors (TLR) respond to microbial stimuli. We studied the effects of ligation of TLR on intestinal epithelial cells (IEC) in preventing an allergic effector response. IEC monolayers (T84 cells) were co-cultured with CD3/28-activated PBMC from healthy controls or atopic patients and simultaneously apically exposed to TLR2, TLR4 or TLR9 ligands. The barrier integrity of T84 cell monolayers was significantly reduced upon co-culture with PBMC of food allergic subjects compared to healthy subjects. Apical exposure of IEC to TLR9, ligand prevented PBMC-induced epithelial barrier disruption. Using PBMC from food allergic subjects, apical TLR9 activation on IEC increased the IFN-γ/IL-13 and IL-10/IL-13 ratio, while suppressing pro-inflammatory IL-6, IL-8 and TNF-α production in an IEC-dependent manner. Hence, activation of apical TLR9 on IEC, potentially by microbiota-derived signals, may play an important role in the prevention of allergic inflammation.
    Clinical Immunology 10/2014; · 3.99 Impact Factor
  • The Journal of infectious diseases. 09/2014;
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    ABSTRACT: Older HIV infected subjects were previously found to have significant B cell expansion during initial antiretroviral therapy in a prospective age-differentiated cohort of older and younger (≥45 vs. ≤30 years) HIV-infected subjects initiating antiretroviral therapy (ART) through the AIDS Clinical Trials Group. Here to further describe this expansion, using a subset of subjects from the same cohort, we characterized B cell phenotypes at baseline and after 192 weeks of ART in both older and younger HIV-infected groups and compared them to uninfected age-matched controls. We also examined whether phenotypes at baseline associated with response to tetanus and hepatitis A vaccine at 12 weeks. Forty six subjects were analyzed in the HIV infected group (21 older, 25 younger) and 30 in the control group (15 per age group). We observed naïve B cells to normalize in younger subjects after 192 weeks of ART, while in older subjects naïve B cells increased to greater levels than those of controls (p = 0.045). Absolute resting memory (RM) cell count was significantly lower in the older HIV infected group at baseline compared to controls and numbers normalized after 192 weeks of ART (p<0.001). Baseline RM cell count positively correlated with week 12 increase in antibody to tetanus vaccine among both younger and older HIV-infected subjects combined (p = 0.01), but not in controls. The age-associated naïve B cell expansion is a novel finding and we discuss several possible explanations for this observation. Relationship between RM cells at baseline and tetanus responses may lead to insights about the effects of HIV infection on B cell memory function and vaccine responses.
    PLoS ONE 09/2014; 9(9):e107064. · 3.53 Impact Factor
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    ABSTRACT: Lactobacillus dominates the lower genital tract microbiota of many women, producing a low vaginal pH, and is important for healthy pregnancy outcomes and protection against several sexually transmitted pathogens. Yet, factors that promote Lactobacillus remain poorly understood. We hypothesized that the amount of free glycogen in the lumen of the lower genital tract is an important determinant of Lactobacillus colonization and a low vaginal pH.
    PLoS ONE 07/2014; 9(7):e102467. · 3.53 Impact Factor
  • Hepatology 07/2014; · 11.19 Impact Factor
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    ABSTRACT: Damage to the intestinal mucosa results in the translocation of microbes from the intestinal lumen into the circulation. Microbial translocation has been proposed to trigger immune activation, inflammation, and coagulopathy, all of which are key factors that drive HIV disease progression and non-HIV comorbidities; however, direct proof of a causal link is still lacking. Here, we have demonstrated that treatment of acutely SIV-infected pigtailed macaques with the drug sevelamer, which binds microbial lipopolysaccharide in the gut, dramatically reduces immune activation and inflammation and slightly reduces viral replication. Furthermore, sevelamer administration reduced coagulation biomarkers, confirming the contribution of microbial translocation in the development of cardiovascular comorbidities in SIV-infected nonhuman primates. Together, our data suggest that early control of microbial translocation may improve the outcome of HIV infection and limit noninfectious comorbidities associated with AIDS.
    Journal of Clinical Investigation 05/2014; · 13.77 Impact Factor
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    ABSTRACT: Previous studies have shown that alterations of the bacterial microbiota in the lower female genital tract influence susceptibility to HIV infection and shedding. We assessed geographic differences in types of genital microbiota between HIV-infected and uninfected women from Rwanda and the United States. Genera of lower genital tract bacterial microbiota were identified by high-throughput pyrosequencing of the 16S rRNA gene from 46 US women (36 HIV-infected, 10 HIV-uninfected) and 40 Rwandan women (18 HIV-infected, 22 HIV-uninfected) with similar proportions of low (0-3) Nugent scores. Species of Lactobacillus were identified by assembling sequences along with reference sequences into phylogenetic trees. Prevalence of genera and Lactobacillus species were compared using Fisher's exact tests. Overall the seven most prevalent genera were Lactobacillus (74%), Prevotella (56%), Gardnerella (55%), Atopobium (42%), Sneathia (37%), Megasphaera (30%), and Parvimonas (26%), observed at similar prevalences comparing Rwandan to US women, except for Megasphaera (20% vs. 39%, p = 0.06). Additionally, Rwandan women had higher frequencies of Mycoplasma (23% vs. 7%, p = 0.06) and Eggerthella (13% vs. 0%, p = 0.02), and lower frequencies of Lachnobacterium (8% vs. 35%, p<0.01) and Allisonella (5% vs. 30%, p<0.01), compared with US women. The prevalence of Mycoplasma was highest (p<0.05) in HIV-infected Rwandan women (39%), compared to HIV-infected US women (6%), HIV-uninfected Rwandan (9%) and US (10%) women. The most prevalent lactobacillus species in both Rwandan and US women was L. iners (58% vs. 76%, p = 0.11), followed by L. crispatus (28% vs. 30%, p = 0.82), L. jensenii (20% vs. 24%, p = 0.80), L. gasseri (20% vs. 11%, p = 0.37) and L. vaginalis (20% vs. 7%, p = 0.10). We found similar prevalence of most major bacterial genera and Lactobacillus species in Rwandan and US women. Further work will be needed to establish whether observed differences differentially impact lower genital tract health or susceptibility to genital infections.
    PLoS ONE 05/2014; 9(5):e96844. · 3.53 Impact Factor
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    ABSTRACT: Poor CD4 lymphocyte recovery on antiretroviral therapy (ART) is associated with reduced function of the thymus. Palifermin (keratinocyte growth factor), by providing support to the thymic epithelium, promotes lymphopoiesis in animal models of bone marrow transplantation and graft-versus-host disease. In AIDS Clinical Trials Group A5212, a randomized, double-blind, placebo-controlled study, 99 HIV-infected patients on ART with plasma HIV-1 RNA levels ≤200 copies/mL for ≥6 months and CD4 lymphocyte counts <200 cells/mm were randomized 1:1:1:1 to receive once daily intravenous administrations of placebo or 20, 40, or 60 µg/kg of palifermin on 3 consecutive days. The median change in CD4 T-cell count from baseline to week 12 was not significantly different between the placebo arm [15 (-16, 23) cells/mm] and the 20-µg/kg dose [11 (2, 32) cells/mm], the 40-µg/kg dose [12 (-2, 25) cells/mm], or the 60-µg/kg dose arm [8 (-13, 35) cells/mm] of palifermin. No significant changes were observed in thymus size or in the number of naïve T cells or recent thymic emigrants. Palifermin in the doses studied was not effective in improving thymic function and did not raise CD4 lymphocyte counts in HIV-infected patients with low CD4 cell counts despite virologically effective ART.
    JAIDS Journal of Acquired Immune Deficiency Syndromes 05/2014; · 4.39 Impact Factor
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    ABSTRACT: Background. Defining the association of non-AIDS-defining events with inflammation and immune activation among HIV-infected persons who are virologically suppressed on antiretroviral therapy (ART) is critical to identifying interventions to decrease their occurrence.Methods. We conducted a case-control study of HIV-infected subjects virologically suppressed after 1 year of ART. Cases had a myocardial infarction, stroke, non-AIDS-defining cancer, serious bacterial infection or death. Controls were matched for age, sex, pre-ART CD4(+)T-cells and regimen. PBMC and plasma from the pre-ART, after 1 year of ART and pre-event time-points were analyzed for activated CD4(+)/CD8(+)T-cells, plasma interleukin-6 (IL-6), soluble tumor necrosis factor receptors (sTNFR)-I and -II, soluble CD14, kynurenine:tryptophan (K/T) ratio and D-dimer. Conditional logistic regression analysis was used to study the association between biomarkers and outcomes with adjustment for potential confounders.Results. Higher levels of IL-6, sTNFR-I and -II, K/T ratio and D-dimer at year 1 were associated with the occurrence of a non-AIDS event. Significant associations were also seen pre-ART and pre-event. Effects remained significant after controlling for confounders. T-cell activation was not significantly related to outcomes.Conclusion. Interventional trials to decrease non-AIDS-defining events among virologically suppressed HIV-infected persons should consider targeting the pathways represented by these soluble markers.
    The Journal of Infectious Diseases 05/2014; · 5.85 Impact Factor
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    ABSTRACT: During HIV infection, IL-10/IL-10 receptor and programmed death-1 (PD-1)/programmed death-1-ligand (PD-L1) interactions have been implicated in the impairment of cytotoxic T lymphocyte (CTL) activity. Despite antiretroviral therapy (ART), attenuated anti-HIV CTL functions present a major hurdle towards curative measures requiring viral eradication. Therefore, deeper understanding of the mechanisms underlying impaired CTL is crucial before HIV viral eradication is viable. The generation of robust CTL activity necessitates interactions between antigen-presenting cells (APC), CD4+ and CD8+ T cells. We have shown that in vitro, IL-10hiPD-L1hi regulatory B cells (Bregs) directly attenuate HIV-specific CD8+-mediated CTL activity. Bregs also modulate APC and CD4+ T cell function; herein we characterize the Breg compartment in uninfected (HIVNEG), HIV-infected "elite controllers" (HIVEC), ART-treated (HIVART), and viremic (HIVvir), subjects, and in vitro, assess the impact of Bregs on anti-HIV CTL generation and activity after reactivation of HIV latent reservoirs using suberoylanilide hydroxamic acid (SAHA). We find that Bregs from HIVEC and HIVART subjects exhibit comparable IL-10 expression levels significantly higher than HIVNEG subjects, but significantly lower than HIVVIR subjects. Bregs from HIVEC and HIVART subjects exhibit comparable PD-L1 expression, significantly higher than in HIVVIR and HIVNEG subjects. SAHA-treated Breg-depleted PBMC from HIVEC and HIVART subjects, displayed enhanced CD4+ T-cell proliferation, significant upregulation of antigen-presentation molecules, increased frequency of CD107a+ and HIV-specific CD8+ T cells, associated with efficient elimination of infected CD4+ T cells, and reduction in integrated viral DNA. Finally, IL-10-R and PD-1 antibody blockade partially reversed Breg-mediated inhibition of CD4+ T-cell proliferation. Our data suggest that, possibly, via an IL-10 and PD-L1 synergistic mechanism; Bregs likely inhibit APC function and CD4+ T-cell proliferation, leading to anti-HIV CTL attenuation, hindering viral eradication.
    PLoS ONE 04/2014; 9(4):e92934. · 3.53 Impact Factor

Publication Stats

11k Citations
1,957.93 Total Impact Points


  • 1988–2015
    • Rush University Medical Center
      • • Department of Immunology and Microbiology
      • • Department of Pediatrics
      • • Department of Internal Medicine
      Chicago, Illinois, United States
  • 2013
    • Utrecht University
      • Division of Pharmacology
      Utrecht, Utrecht, Netherlands
    • University of Iowa
      • Department of Internal Medicine
      Iowa City, IA, United States
  • 2011–2013
    • University of California, San Francisco
      San Francisco, California, United States
    • University College London
      • Department of Infection and Population Health
      London, ENG, United Kingdom
  • 1998–2013
    • National Cancer Institute (USA)
      • Experimental Immunology Branch
      베서스다, Maryland, United States
  • 2012
    • University of Melbourne
      • Department of Microbiology and Immunology
      Melbourne, Victoria, Australia
  • 2011–2012
    • Burnet Institute
      • Centre for Virology
      Melbourne, Victoria, Australia
    • Albert Einstein College of Medicine
      • Department of Epidemiology & Population Health
      New York City, NY, United States
  • 1999–2012
    • Case Western Reserve University School of Medicine
      • Department of Pathology
      Cleveland, OH, United States
  • 1995–2012
    • University of Illinois at Chicago
      • Department of Pediatrics (Chicago)
      Chicago, Illinois, United States
    • University of Chicago
      • Department of Microbiology
      Chicago, IL, United States
  • 2001–2011
    • CSU Mentor
      Long Beach, California, United States
    • Harvard University
      Cambridge, Massachusetts, United States
    • Northwestern Memorial Hospital
      Chicago, Illinois, United States
  • 2010
    • Virginia Commonwealth University
      Richmond, Virginia, United States
    • University of Southern California
      • Keck School of Medicine
      Los Angeles, California, United States
    • Harvard Medical School
      Boston, Massachusetts, United States
    • University of California, Davis
      • Division of Infectious and Immunologic Diseases
      Davis, California, United States
  • 1998–2010
    • Case Western Reserve University
      • • Division of Hospital Medicine (MetroHealth Medical Center)
      • • Division of Infectious Diseases and HIV Medicine
      • • Center for AIDS Research
      • • MetroHealth Medical Center
      Cleveland, OH, United States
  • 2009
    • University of Western Australia
      • School of Pathology and Laboratory Medicine
      Perth, Western Australia, Australia
    • National Institute of Allergy and Infectious Diseases
      • Laboratory of Immunoregulation
      Maryland, United States
  • 2007–2009
    • University of California, Los Angeles
      Los Angeles, California, United States
  • 1988–2009
    • Rush Medical College
      Chicago, Illinois, United States
  • 1998–2007
    • Karolinska Institutet
      • Institutionen för medicin, Huddinge
      Solna, Stockholm, Sweden
  • 2006
    • University of Antioquia
      • Facultad de Medicina
      Santa Fe de Antioquia, Antioquia, Colombia
    • Vanderbilt University
      • Center for Human Genetics Research (CHGR)
      Nashville, MI, United States
  • 2005
    • University of Maryland, Baltimore
      • Institute of Human Virology
      Baltimore, MD, United States
  • 2004
    • Beth Israel Medical Center
      New York City, New York, United States
  • 1998–2003
    • University of Washington Seattle
      • Division of Allergy and Infectious Diseases
      Seattle, Washington, United States
  • 1988–2003
    • Dana-Farber Cancer Institute
      Boston, Massachusetts, United States
  • 2002
    • University of Texas Medical Branch at Galveston
      • Department of Internal Medicine
      Galveston, Texas, United States
  • 2000
    • University of North Carolina at Chapel Hill
      North Carolina, United States
    • Beth Israel Deaconess Medical Center
      • Division of Viral Pathogenesis
      Boston, MA, United States
  • 1991–2000
    • National Institutes of Health
      • Branch of Experimental Immunology
      Bethesda, MD, United States
    • University of Wisconsin, Madison
      • Department of Human Oncology
      Madison, MS, United States
  • 1996
    • University of Milan
      Milano, Lombardy, Italy
  • 1989
    • Aurora St. Luke's Medical Center
      Milwaukee, Wisconsin, United States