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1. Single center, open label dose escalating trial evaluating once weekly oral ixazomib in ART-suppressed, HIV positive adults and effects on HIV reservoir size in vivo

Author

Cummins, Nathan W, Baker, Jason, Chakraborty, Rana, Dean, Patrick G, Garcia-Rivera, Enrique, Krogman, Ashton, Kumar, Shaji, Kuzmichev, Yury V, Laird, Gregory M, Landay, Alan, Lichterfeld, Mathias, Mahmood, Maryam, Martinson, Jeffrey, Maynes, Mark, Natesampillai, Sekar, Rajkumar, Vincent, Rassadkina, Yelizaveta, Ritter, Kristen D., Rivera, Christina G, Rizza, Stacey A, Subramanian, Krupa, Tande, Aaron J, Wonderlich, Elizabeth R, Whitaker, Jennifer A, Zeuli, John, and Badley, Andrew D

Published
2021
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2. Association of Chronic Hepatitis C Infection With T-Cell Phenotypes in HIV-Negative and HIV-Positive Women

Author

Kuniholm, Mark H, Xie, Xianhong, Anastos, Kathryn, Kaplan, Robert C, Xue, Xiaonan, Kovacs, Andrea, Peters, Marion G, Seaberg, Eric C, French, Audrey L, Young, Mary A, Augenbraun, Michael, Martinson, Jeffrey A, Bush, Kristin A, Landay, Alan L, and Strickler, Howard D

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Emerging Infectious Diseases, HIV/AIDS, Hepatitis, Chronic Liver Disease and Cirrhosis, Liver Disease, Clinical Research, Hepatitis - C, Digestive Diseases, Infectious Diseases, Infection, Good Health and Well Being, Adolescent, Adult, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, CD8-Positive T-Lymphocytes, Female, HIV Seronegativity, HIV Seropositivity, Hepatitis C, Chronic, Humans, Immunity, Cellular, Middle Aged, Multivariate Analysis, T-Lymphocyte Subsets, Viral Load, Young Adult, hepatitis C virus, HIV, T cell, phenotype, activation, differentiation, Clinical Sciences, Public Health and Health Services, Virology, Clinical sciences, Epidemiology, Public health
Abstract

BackgroundHepatitis 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).MethodsWe used fresh blood from HIV-positive and at-risk HIV-negative women, with and without chronic HCV, to measure percentages of activated CD4⁺ and CD8⁺ T cells, Tregs, and T-cell differentiation phenotypes (naive, central memory, effector memory (EM), and terminally differentiated effector). This included 158 HIV negatives and 464 HIV positives, of whom 18 and 63, respectively, were HCV viremic.ResultsIn multivariate models of HIV negatives, HCV viremia was associated with 25% fewer naive CD4⁺ (P = 0.03), 33% more EM CD4⁺ (P = 0.0002), and 37% fewer central memory CD8⁺ (P = 0.02) T cells. Among HIV positives, we observed only 1 of these 3 relationships: higher percentage of EM CD4⁺ among HCV viremic women. Furthermore, the association with EM CD4⁺ among HIV positives was limited to individuals with diminished immune status (total CD4⁺ count ≤500 cells/μL), as were associations of HCV viremia with higher percentages of activated CD4⁺ and Tregs. Among HIV positives with high CD4⁺ count, no significant associations were observed.ConclusionsThese data suggest that HCV viremia in HIV negatives is associated with accelerated T-cell differentiation, but among HIV positives, the impact of HCV viremia is less straightforward and varies by total CD4v count.

Published
2014

3. The Relation of Plasmacytoid Dendritic Cells (pDCs) and Regulatory T-Cells (Tregs) with HPV Persistence in HIV-Infected and HIV-Uninfected Women

Author

Strickler, Howard D, Martinson, Jeffrey, Desai, Seema, Xie, Xianhong, Burk, Robert D, Anastos, Kathryn, Massad, L Stewart, Minkoff, Howard, Xue, Xiaonan, D'Souza, Gypsyamber, Levine, Alexandra M, Colie, Christine, Watts, D Heather, Palefsky, Joel M, and Landay, Alan

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Immunology, Clinical Research, Women's Health, HIV/AIDS, Infectious Diseases, Immunotherapy, Cervical Cancer, Sexually Transmitted Infections, Prevention, Cancer, Aetiology, 2.1 Biological and endogenous factors, Infection, Adult, CD4 Lymphocyte Count, CD4-Positive T-Lymphocytes, Chronic Disease, Dendritic Cells, Female, HIV Infections, Humans, Papillomavirus Infections, Pilot Projects, T-Lymphocytes, Regulatory, Uterine Cervical Neoplasms, Virology
Abstract

Other than CD4+ count, the immunologic factors that underlie the relationship of HIV/AIDS with persistent oncogenic HPV (oncHPV) and cervical cancer are not well understood. Plasmacytoid dendritic cells (pDCs) and regulatory T-cells (Tregs) are of particular interest. pDCs have both effector and antigen presenting activity and, in HIV-positive patients, low pDC levels are associated with opportunistic infections. Tregs downregulate immune responses, and are present at high levels in HIV-positives. The current pilot study shows for the first time that low pDC and high Treg levels may be significantly associated with oncHPV persistence in both HIV-positive and HIV-negative women. Larger studies are now warranted.

Published
2014

4. A low T regulatory cell response may contribute to both viral control and generalized immune activation in HIV controllers.

Author

Hunt, Peter W, Landay, Alan L, Sinclair, Elizabeth, Martinson, Jeffrey A, Hatano, Hiroyu, Emu, Brinda, Norris, Philip J, Busch, Michael P, Martin, Jeffrey N, Brooks, Cicely, McCune, Joseph M, and Deeks, Steven G

Subjects
Cytomegalovirus, HIV, Viremia, HIV Infections, Case-Control Studies, Lymphocyte Activation, Immunity, T-Cell Antigen Receptor Specificity, Models, Immunological, T-Lymphocytes, Regulatory, Models, Immunological, T-Lymphocytes, Regulatory, General Science & Technology
Abstract

HIV-infected individuals maintaining undetectable viremia in the absence of therapy (HIV controllers) often maintain high HIV-specific T cell responses, which has spurred the development of vaccines eliciting HIV-specific T cell responses. However, controllers also often have abnormally high T cell activation levels, potentially contributing to T cell dysfunction, CD4+ T cell depletion, and non-AIDS morbidity. We hypothesized that a weak T regulatory cell (Treg) response might contribute to the control of viral replication in HIV controllers, but might also contribute to generalized immune activation, contributing to CD4+ T cell loss. To address these hypotheses, we measured frequencies of activated (CD38+ HLA-DR+), regulatory (CD4+CD25+CD127(dim)), HIV-specific, and CMV-specific T cells among HIV controllers and 3 control populations: HIV-infected individuals with treatment-mediated viral suppression (ART-suppressed), untreated HIV-infected "non-controllers" with high levels of viremia, and HIV-uninfected individuals. Despite abnormally high T cell activation levels, controllers had lower Treg frequencies than HIV-uninfected controls (P = 0.014). Supporting the propensity for an unusually low Treg response to viral infection in HIV controllers, we observed unusually high CMV-specific CD4+ T cell frequencies and a strong correlation between HIV-specific CD4+ T cell responses and generalized CD8+ T cell activation levels in HIV controllers (P ≤ 0.001). These data support a model in which low frequencies of Tregs in HIV controllers may contribute to an effective adaptive immune response, but may also contribute to generalized immune activation, potentially contributing to CD4 depletion.

Published
2011

6. Reply to Itzhaki and Klapper

Author

Lurain, Nell S., Hanson, Barbara A., Martinson, Jeffrey, Leurgans, Sue E., Landay, Alan L., Bennett, David A., and Schneider, Julie A.

Published
2014

12. Upregulated IL-32 Expression And Reduced Gut Short Chain Fatty Acid Caproic Acid in People Living With HIV With Subclinical Atherosclerosis

Author

El-Far, Mohamed, primary, Durand, Madeleine, additional, Turcotte, Isabelle, additional, Larouche-Anctil, Etienne, additional, Sylla, Mohamed, additional, Zaidan, Sarah, additional, Chartrand-Lefebvre, Carl, additional, Bunet, Rémi, additional, Ramani, Hardik, additional, Sadouni, Manel, additional, Boldeanu, Irina, additional, Chamberland, Annie, additional, Lesage, Sylvie, additional, Baril, Jean-Guy, additional, Trottier, Benoit, additional, Thomas, Réjean, additional, Gonzalez, Emmanuel, additional, Filali-Mouhim, Ali, additional, Goulet, Jean-Philippe, additional, Martinson, Jeffrey A., additional, Kassaye, Seble, additional, Karim, Roksana, additional, Kizer, Jorge R., additional, French, Audrey L., additional, Gange, Stephen J., additional, Ancuta, Petronela, additional, Routy, Jean-Pierre, additional, Hanna, David B., additional, Kaplan, Robert C., additional, Chomont, Nicolas, additional, Landay, Alan L., additional, and Tremblay, Cécile L., additional

Published
2021
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14. Potential inflammatory consequences in HIV controllers

Author

Martin Jeffrey N, Busch Michael P, Norris Philip J, Emu Brinda, Hatano Hiroyu, Martinson Jeffrey A, Landay Alan L, Hsue Priscilla Y, Sinclair Elizabeth, Hunt Peter W, Brooks Cecily, McCune Joseph M, and Deeks Steven G

Subjects
Immunologic diseases. Allergy, RC581-607
Published
2010
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19. Abstract 404: Prognostic value of soluble and cell surface immune-checkpoint molecules in advanced non-small cell lung cancer (NSCLC) patients receiving anti-PD-1/-L1 immunotherapy

Author

Tarhoni, Imad, primary, Fidler, Mary Jo, additional, Fughhi, Ibtihaj, additional, Wakefield, Connor, additional, Kollipara, Revathi, additional, Multani, Maneet, additional, Batus, Marta, additional, Basu, Sanjib, additional, Lie, Wen-Rong, additional, Russell, Donna, additional, Martinson, Jeffrey, additional, Landay, Alan L., additional, Kuzel, Timothy M., additional, Bonomi, Philip, additional, and Borgia, Jeffrey A., additional

Published
2019
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20. Polymorphism rs1385129 Within Glut1 Gene SLC2A1 Is Linked to Poor CD4+ T Cell Recovery in Antiretroviral-Treated HIV+ Individuals

Author

Masson, Jesse J. R., primary, Cherry, Catherine L., additional, Murphy, Nicholas M., additional, Sada-Ovalle, Isabel, additional, Hussain, Tabinda, additional, Palchaudhuri, Riya, additional, Martinson, Jeffrey, additional, Landay, Alan L., additional, Billah, Baki, additional, Crowe, Suzanne M., additional, and Palmer, Clovis S., additional

Published
2018
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22. Vitamin D does not Modulate Immune-Mediated Bone loss during ART Initiation

Author

Yin, Michael T, Chan, Ellen S, Brown, Todd T, Kinslow, Jennifer, Martinson, Jeffrey, Landay, Alan, Melbourne, Kathleen M, Ribaudo, Heather J, and Overton, Edgar T

Abstract

Background Vitamin D (VitD) and calcium (Ca) supplementation attenuates antiretroviral therapy (ART)-associated bone loss, but it is unclear whether this effect is mediated through immunomodulation.Methods In this exploratory analysis of A5280, a 48-week, randomized, double-blind, placebo-controlled study of VitD/Ca supplementation with ART initiation, we characterized lymphocyte phenotypes and receptor activator of nuclear factor kappa-B ligand (RANKL) expression by median fluorescence intensity (MFI) at baseline and 48 weeks. Changes were evaluated within and between treatment groups by Wilcoxon signed rank and rank sum tests, respectively. Spearman correlations estimated relationships between cellular phenotypes and bone mineral density (BMD).Results Of 165 participants enrolled, 138 had samples for cellular phenotypes (64 VitD/Ca, 74 placebo). Markers of CD4, CD8 activation (CD38+HLA-DR+) declined (all P<0.001), but did not differ between arms. There was no decline in either %T-cells (CD4 and CD8) expressing RANKL or expression of RANKL by MFI. CD4 and CD8 activation markers were not correlated with BMD at baseline (r<0.15 and P>0.09 for all), but greater declines in CD4 activation correlated with greater declines in hip and spine BMD in both arms (0.25 =r =0.37, all P<0.05). A greater decline in CD8 activation was correlated with greater declines in both hip and spine BMD in the placebo arm only (hip r=0.31, P=0.009; spine r=0.25, P=0.035).Conclusions Reductions in T-cell activation are characteristic of ART initiation, but only correlated modestly with bone loss. VitD/Ca supplementation does not appear to mitigate bone loss through modulation of immune activation or expression of RANKL. Trial registration number: NCT01403051.

Published
2019
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25. Optimizing Viable Leukocyte Sampling from the Female Genital Tract for Clinical Trials: An International Multi-Site Study

Author

McKinnon, Lyle R., primary, Hughes, Sean M., additional, De Rosa, Stephen C., additional, Martinson, Jeffrey A., additional, Plants, Jill, additional, Brady, Kirsten E., additional, Gumbi, Pamela P., additional, Adams, Devin J., additional, Vojtech, Lucia, additional, Galloway, Christine G., additional, Fialkow, Michael, additional, Lentz, Gretchen, additional, Gao, Dayong, additional, Shu, Zhiquan, additional, Nyanga, Billy, additional, Izulla, Preston, additional, Kimani, Joshua, additional, Kimwaki, Steve, additional, Bere, Alfred, additional, Moodie, Zoe, additional, Landay, Alan L., additional, Passmore, Jo-Ann S., additional, Kaul, Rupert, additional, Novak, Richard M., additional, McElrath, M. Juliana, additional, and Hladik, Florian, additional

Published
2014
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29. Potential inflammatory consequences in HIV controllers

Author

Hunt, Peter W, primary, Hsue, Priscilla Y, additional, Sinclair, Elizabeth, additional, Landay, Alan L, additional, Martinson, Jeffrey A, additional, Hatano, Hiroyu, additional, Emu, Brinda, additional, Norris, Philip J, additional, Busch, Michael P, additional, Martin, Jeffrey N, additional, Brooks, Cecily, additional, McCune, Joseph M, additional, and Deeks, Steven G, additional

Published
2010
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37. Dendritic cells from HIV-1 infected individuals are less responsive to toll-like receptor (TLR) ligands

Author

Martinson, Jeffrey A., primary, Roman-Gonzalez, Alejandro, additional, Tenorio, Allan R., additional, Montoya, Carlos J., additional, Gichinga, Carolyne N., additional, Rugeles, Maria T., additional, Tomai, Mark, additional, Krieg, Arthur M., additional, Ghanekar, Smita, additional, Baum, Linda L., additional, and Landay, Alan L., additional

Published
2007
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41. Searching for Bellwethers: Examining Representations of Northern Irish, Palestinian, and Israeli Leaders.

Author

Grove, Andrea K., Martinson, Jeffrey D., and Sylvan, Donald A.

Subjects
*INTERNATIONAL conflict, *LEADERS, *POLITICAL leadership, *INTERGROUP relations
Abstract

Growing out of their work on the impact of problem representations on the Israeli-Palestinian and Northern Ireland conflicts, the authors examine the phenomenon of leaders representing intergroup relationships differently to disparate audiences. Drawing on literature from psychology, political science, and communications, this paper studies both the patterns and the impact of representations by specific leaders in these complex, conflicts. [ABSTRACT FROM AUTHOR]

Published
2004

47. Immunocytochemistry and flow cytometry evaluation of human megakaryocytes in fresh samples and cultures of CD34+ cells

Author

Qiao, Xiaoying, primary, Loudovaris, Maureen, additional, Unverzagt, Kristen, additional, Walker, Donald E., additional, Smith, Stephen L., additional, Martinson, Jeffrey, additional, Schilling, Marta, additional, Lee, Wanda, additional, Williams, Stephanie F., additional, Van Epps, Dennis E., additional, Cohen, Isaac, additional, and Bender, James G., additional

Published
1996
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49. Regulatory B cell frequency correlates with markers of HIV disease progression and attenuates anti‐HIV CD8+T cell function in vitro

Author

Siewe, Basile, Stapleton, Jack T., Martinson, Jeffrey, Keshavarzian, Ali, Kazmi, Nazia, Demarais, Patricia M., French, Audrey L., and Landay, Alan

Abstract

A role for regulatory B cells is shown in HIV‐pathogenesis, potentially impacting HIV cell‐mediated control. HIV infection is associated with elevated expression of IL‐10 and PD‐L1, contributing to impairment of T cell effector functions. In autoimmunity, tumor immunology, and some viral infections, Bregs modulate T cell function via IL‐10 production. In this study, we tested the hypothesis that during HIV infection, Bregs attenuate CD8+T cell effector function, contributing to immune dysfunction. We determined that in vitro, TLR2‐, TLR9‐, and CD40L‐costimulated Bregs from HIV−individuals exhibited a high frequency of cells expressing IL‐10 and PD‐L1. Compared with Bregs from HIV−individuals, a significantly higher percentage of Bregs from HIV+individuals spontaneously expressed IL‐10 (P=0.0218). After in vitro stimulation with HIV peptides, Breg‐depleted PBMCs from HIV+individuals exhibited a heightened frequency of cytotoxic (CD107a+; P=0.0171) and HIV‐specific CD8+T cells compared with total PBMCs. Furthermore, Breg depletion led to enhanced proliferation of total CD8+and CD107a+CD8+T cells (P=0.0280, and P=0.0102, respectively). In addition, augmented CD8+T cell effector function in vitro was reflected in a 67% increased clearance of infected CD4+T cells. The observed Breg suppression of CD8+T cell proliferation was IL‐10‐dependent. In HIV+individuals, Breg frequency correlated positively with viral load (r=0.4324; P=0.0095), immune activation (r=0.5978; P=0.0005), and CD8+T cell exhaustion (CD8+PD‐1+; r=0.5893; P=0.0101). Finally, the frequency of PD‐L1‐expressing Bregs correlated positively with CD8+PD‐1+T cells (r=0.4791; P=0.0443). Our data indicate that Bregs contribute to HIV‐infection associated immune dysfunction by T cell impairment, via IL‐10 and possibly PD‐L1 expression.

Published
2013
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50. Potent HIV-specific responses are enriched in a unique subset of CD8+T cells that coexpresses CD4 on its surface

Author

Zloza, Andrew, Schenkel, Jason M., Tenorio, Allan R., Martinson, Jeffrey A., Jeziorczak, Paul M., and Al-Harthi, Lena

Abstract

In humans, approximately 3% of peripheral CD8+T cells coexpress CD4 dimly on their surface and hence are designated as CD4dimCD8brightT cells. We evaluated the contribution of this CD4dimCD8brightT-cell population to anti-HIV immunity. We demonstrate that CD4dimCD8brightT cells generate greater than 55% of CD8+T-cell antigen recognition and effector response to HIV, as evaluated by multiple parameters for assessing T-cell antiviral immunity, including HIV tetramer recognition, cytokine production, and cytolytic potential. Inhibition of major histocompatibility class II (MHC-II) on target cells or CD4 on CD4dimCD8brightT cells diminishes their anti-HIV responses, suggesting that CD4 on effector cells and MHC-II on target cells provides an additional arm of contact between effector and target cells which is critical to CD4dimCD8brightT-cell function. CD4dimCD8brightT cells also exhibit features that are indicative of central memory T cells. Finally, CD4dimCD8brightT cells are elevated in blood of HIV+long-term nonprogressors in comparison to HIV−donors. Collectively, our findings show that CD4dimCD8brightT cells designate an enriched antiviral subpopulation of CD8+T cells that should be targeted for therapeutic intervention or evaluation of vaccine efficacy.

Published
2009
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