The role of cytokines in the pathogenesis and treatment of HIV infection
Section snippets
Pathogenesis of HIV infection
HIV infection targets the immune system leading to a state of immunodeficiency in a setting of immune activation. The molecular mechanisms causing the pathogenesis of HIV infection are still incompletely understood and are probably a composite of multiple factors. The acute phase of HIV infection or SIV infected rhesus macaques (RM) is characterized by a substantial drop in peripheral CD4 T cell counts and a substantial depletion of memory CD4+ CCR5+ T cells [1], [2], [3], [4], [5]. In the
T cell immune activation
It is likely that multiple forces are responsible for the disruption of the immune systems of patients with HIV infection (Fig. 1). An unresolved paradox in patients with HIV infection is that while both CD4 and CD8 T cells are activated, one sees depletion of the CD4 T cell pool and expansion of the CD8 T cell pool. A direct cytopathic effect of HIV infection on CD4 T cells may explain part of this difference, however, the low number of cells actively infected at any given point makes this an
Cytokine and immune activation pathways
In the course of chronic HIV infection, homeostatic forces and HIV-induced inflammation differentially affect CD4 and CD8 T cell immune activation. These differences are reflected in the ways that these T cell pools respond to the inflammatory and homeostatic environments (Fig. 1).
Inflammation and biomarkers: IL-6, sCD14 and D-dimer
The introduction of cART has improved the life expectancy of HIV infected individuals. While antiretroviral therapies are capable of suppressing plasma levels of HIV to <50 copies/ml for extended periods of time, levels of viral replication return to baseline within weeks of stopping therapy and thus patients with HIV infection today face the likelihood of life-long therapy. An increasing body of data are clearly demonstrating that despite plasma levels of HIV that are “undetectable” there is
Dr. Marta Catalfamo received a Biochemistry degree at the National University of Tucuman. Argentina. She obtained her PhD degree in Immunology from the Autonomous University of Barcelona, Spain. She did her postdoctoral studies in human CD4 and CD8 T cell function, and she defined a new regulated secretory pathways for the chemokine RANTES. After completing her post-doctoral training at the National Cancer Institute, NIH, she joined as staff scientist at the Laboratory of Immunoregulation at
References (106)
- et al.
Immune activation set point during early HIV infection predicts subsequent CD4+ T-cell changes independent of viral load
Blood
(2004) - et al.
Viral and host factors in the pathogenesis of HIV infection
Current Opinion in Immunology
(2005) - et al.
Homeostasis of naive and memory T cells
Immunity
(2008) - et al.
Lymphocyte kinetics in health and disease
Trends in Immunology
(2009) - et al.
A potential role for interleukin-7 in T-cell homeostasis
Blood
(2001) - et al.
Restoration of T-cell homeostasis after T-cell depletion
Seminars in Immunology
(1997) - et al.
Idiopathic CD4+ T lymphocytopenia is associated with increases in immature/transitional B cells and serum levels of IL-7
Blood
(2007) - et al.
Distinctions between CD8+ and CD4+ T-cell regenerative pathways result in prolonged T-cell subset imbalance after intensive chemotherapy
Blood
(1997) - et al.
Differential effects of HIV viral load and CD4 count on proliferation of naive and memory CD4 and CD8 T lymphocytes
Blood
(2011) - et al.
Maintenance of peripheral naive T cells is sustained by thymus output in mice but not humans
Immunity
(2012)
Interleukin-7: from bench to clinic
Blood
Cytokine signaling in 2002: new surprises in the Jak/Stat pathway
Cell
Priming of T cells to Fas-mediated proliferative signals by interleukin-7
Blood
Lymph node architecture collapse and consequent modulation of FOXO3a pathway on memory T- and B-cells during HIV infection
Seminars in Immunology
IL-7 administration drives T cell-cycle entry and expansion in HIV-1 infection
Blood
IL-15 delays suppression and fails to promote immune reconstitution in virally suppressed chronically SIV-infected macaques
Blood
IL-15 administered by continuous infusion to rhesus macaques induces massive expansion of CD8+ T effector memory population in peripheral blood
Blood
HIV-1 immunopathogenesis: how good interferon turns bad
Clinical Immunology
HIV inhibits CD4+ T-cell proliferation by inducing indoleamine 2,3-dioxygenase in plasmacytoid dendritic cells
Blood
Gastrointestinal tract as a major site of CD4+ T cell depletion and viral replication in SIV infection
Science (New York, NY)
CD4+ T cell depletion during all stages of HIV disease occurs predominantly in the gastrointestinal tract
The Journal of Experimental Medicine
Primary HIV-1 infection is associated with preferential depletion of CD4+ T lymphocytes from effector sites in the gastrointestinal tract
The Journal of Experimental Medicine
Peak SIV replication in resting memory CD4+ T cells depletes gut lamina propria CD4+ T cells
Nature
Massive infection and loss of memory CD4+ T cells in multiple tissues during acute SIV infection
Nature
Few infected CD4+ T cells but a high proportion of replication-competent provirus copies in asymptomatic human immunodeficiency virus type 1 infection
Journal of Virology
Quantitative image analysis of HIV-1 infection in lymphoid tissue
Science (New York, NY)
Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection
Nature
Population biology of HIV-1 infection: viral and CD4+ T cell demographics and dynamics in lymphatic tissues
Annual Review of Immunology
Abnormalities of B-cell activation and immunoregulation in patients with the acquired immunodeficiency syndrome
The New England Journal of Medicine
Immunologic abnormalities in the acquired immunodeficiency syndrome
Annual Review of Immunology
AIDS as immune system activation: a model for pathogenesis
Clinical and Experimental Immunology
Shorter survival in advanced human immunodeficiency virus type 1 infection is more closely associated with T lymphocyte activation than with plasma virus burden or virus chemokine coreceptor usage
The Journal of Infectious Diseases
HIV preferentially infects HIV-specific CD4+ T cells
Nature
CD8+ T cells specific for EBV, cytomegalovirus, and influenza virus are activated during primary HIV infection
Journal of Immunology
NK cells in HIV infection: paradigm for protection or targets for ambush
Nature Reviews
HIV disease: fallout from a mucosal catastrophe?
Nature Immunology
Loss of memory B cells during chronic HIV infection is driven by Foxo3a- and TRAIL-mediated apoptosis
The Journal of Clinical Investigation
Impact of HIV-1 infection and highly active antiretroviral therapy on the kinetics of CD4+ and CD8+ T cell turnover in HIV-infected patients
Proceedings of the National Academy of Sciences of the United States of America
Factors influencing T-cell turnover in HIV-1-seropositive patients
The Journal of Clinical Investigation
Identification of dynamically distinct subpopulations of T lymphocytes that are differentially affected by HIV
The Journal of Experimental Medicine
Limited CD4 + T-cell renewal in early HIV-1 infection: effect of highly active antiretroviral therapy
Nature Medicine
T cell depletion in HIV-1 infection: how CD4 + T cells go out of stock
Nature Immunology
Circulating HIV-specific CD8+ cytotoxic T cells express CD38 and HLA-DR antigens
Journal of Immunology
Selective increase of activation antigens HLA-DR and CD38 on CD4+ CD45RO+ T lymphocytes during HIV-1 infection
Clinical and Experimental Immunology
T cell activation and disease severity in HIV infection
Clinical and Experimental Immunology
Persistent immune activation in HIV-1 infection is associated with progression to AIDS
AIDS (London, England)
Severe depletion of mucosal CD4+ T cells in AIDS-free simian immunodeficiency virus-infected sooty mangabeys
Journal of Immunology
Acute loss of intestinal CD4+ T cells is not predictive of simian immunodeficiency virus virulence
Journal of Immunology
Natural SIV hosts: showing AIDS the door
Science (New York, NY)
Inflammatory and coagulation biomarkers and mortality in patients with HIV infection
PLoS Medicine
Cited by (74)
A novel QCM immunosensor development based on gold nanoparticles functionalized sulfur-doped graphene quantum dot and h-ZnS-CdS NC for Interleukin-6 detection
2021, Analytica Chimica ActaCitation Excerpt :In addition, IL-6 has valuable role on metabolism responsible for glucose intake and insulin activity [4]. Moreover, its overexpression has been investigated in some tumor cells corresponding to microenvironment and immunomodulation [5]. When many scientists want to show the effects of high IL-6 concentration, they can find the direct link between inflammation and cancer on the basis of IL-6 concentration [2].
Plasma Cytokine Expression and Immune Reconstitution in Early and Delayed Anti-HIV 96-Weeks Treatment: A Retrospective Study
2024, AIDS Research and Human RetrovirusesPlasma IL-33 levels and immune activation in HIV-TB coinfection: a cross-sectional study in Yaoundé, Cameroon
2023, Pan African Medical JournalPacritinib Inhibition of IRAK1 Blocks Aberrant TLR8 Signalling by SARS-CoV-2 and HIV-1-Derived RNA
2023, Journal of Innate Immunity
Dr. Marta Catalfamo received a Biochemistry degree at the National University of Tucuman. Argentina. She obtained her PhD degree in Immunology from the Autonomous University of Barcelona, Spain. She did her postdoctoral studies in human CD4 and CD8 T cell function, and she defined a new regulated secretory pathways for the chemokine RANTES. After completing her post-doctoral training at the National Cancer Institute, NIH, she joined as staff scientist at the Laboratory of Immunoregulation at NIAID, NIH. Her research focuses in understanding the cytokine-driven mechanisms of immune activation during HIV infection. Her work has delineated clear differences in the activation of CD4 and CD8 T cell pools in patients with HIV infection. Her studies are directed to address how the homeostatic response to CD4 T cell depletion and the inflammatory response to HIV infection affect the immune activation of CD4 and CD8 T cell subsets. Particularly, the interactions of the signaling pathways between IL-7 and Type I IFNs associated with these two environments.
Dr. Cecile Le Saout obtained her Master's degree in Biology and Health in 2005 and her PhD degree in Immunology in 2009, from the University of Montpellier II, France. She joined the Laboratory of Immunoregulation at the National Institute of Allergy and Infectious Diseases, NIH for post-doctoral training in 2010. Her research is focused on elucidating the molecular mechanisms of T cell immune activation during HIV infection, particularly the cross-talk between the cytokines associated with the homeostatic (IL-7) and the inflammatory (Type-I IFN) environments induced by HIV infection.
H. Clifford Lane received his M.D. degree from the University of Michigan in 1976. He then completed an internship and residency at the University of Michigan Hospital, Ann Arbor, Michigan. In 1979, he came to the National Institutes of Health (NIH) as a clinical associate in the Laboratory of Immunoregulation (LIR) of the National Institute of Allergy and Infectious Diseases (NIAID). He is currently chief of the Clinical and Molecular Retrovirology Section of the LIR and the clinical director, director of the Division of Clinical Research and Deputy Director for Clinical Research and Special Projects of NIAID.
He became one of the first investigators to study immunopathogenic mechanisms of HIV disease, ultimately making a series of observations that helped establish the field of HIV immunopathogenesis. In the clinical arena, he has studied innovative approaches to therapy and has used experimental therapeutic interventions as a means of furthering our understanding of HIV pathogenesis. Among other things, he has investigated the strategies of syngeneic bone marrow transplantation, adoptive transfer of lymphocytes, and role of the cytokines alpha interferon and IL-2 in the treatment of patients with HIV infection.
- 1
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Bldg 10 Room 11B07, Bethesda, MD 20892-1360, United States. Tel.: +1 301 443 8313; fax: +1 301 402 4097.
- 2
Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, 10 Center Drive, Rm. 4-1479, MSC 1460, Bethesda, MD 20892-1360, United States. Tel.: +1 301 4966572; fax: +1 301 480 5560.