The role of the T-helper/T-suppressor ratio in the adaptive immune response: a dynamical model

Recent experimental studies have suggested the ratio between T-helper and T-suppressor lymphocytes as an index of immunosuppression in HIV, cancer, immunosenescence and inflammatory and auto-immune diseases. However, a quantitative understanding of the impact of this ratio on the immune response has lagged behind data and its validity as a tool for prognostic monitoring or therapeutic target remains an open question. In this work, we use statistical physics and dynamical systems approaches to analyze the time-dependent response to an antigen, of a simplified model of the adaptive immune system, which comprises B, T-helper and T-suppressor lymphocytes. The model is remarkably robust against changes in the noise level and kinetic parameters, but it is very sensitive to changes in the ratio between T-helper and T-suppressor lymphocytes, exhibiting, in particular, a transition from a responsive to an immuno-suppressed phase, as the ratio is lowered below a critical value, which is in line with experiments. This result supports the validity of the T-helper/T-suppressor ratio as an index of immunosuppression and may provide a useful theoretical benchmark to interpret and compare experiments.

• Publication year

  2017

• Venue

  Journal of Physics A: Mathematical and Theoretical

• Publication date

  2017-01-26

• Fields of study

  Biology, Medicine, Physics

• Identifiers
  DOI 10.1088/1751-8121/aaed5earXiv 1701.07712
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar

• No claims are published for this paper.

• No concepts are published for this paper.

• Immunology

  2020cited by this paper
• Journal of Surgical Oncology

  2017cited by this paper
• Imbalance in the game of T cells: What can the CD4/CD8 T-cell ratio tell us about HIV and health?

  2017cited by this paper
• Could Lymphocyte Profiling be Useful to Diagnose Systemic Autoimmune Diseases?

  2017cited by this paper
• The distribution of bacterial doubling times in the wild

  2017cited by this paper
• CD4:CD8 Ratio and CD8 Count as Prognostic Markers for Mortality in Human Immunodeficiency Virus–Infected Patients on Antiretroviral Therapy: The Antiretroviral Therapy Cohort Collaboration (ART-CC)

  2017cited by this paper
• A Sigmoid Functional Response Emerges When Cytotoxic T Lymphocytes Start Killing Fresh Target Cells

  2017cited by this paper
• A Population Dynamics Model for Clonal Diversity in a Germinal Center

  2017cited by this paper
• Microbes and Infection

  2017cited by this paper
• The role of idiotypic interactions in the adaptive immune system: a belief-propagation approach

  2016cited by this paper
• How many TCR clonotypes does a body maintain?

  2016cited by this paper
• Maximum-Entropy Models of Sequenced Immune Repertoires Predict Antigen-Antibody Affinity

  2016cited by this paper
• BIITE: A Tool to Determine HLA Class II Epitopes from T Cell ELISpot Data

  2016cited by this paper
• Statistical mechanics of clonal expansion in lymphocyte networks modelled with slow and fast variables

  2016cited by this paper
• High levels of regulatory T cells in blood are a poor prognostic factor in patients with diffuse large B-cell lymphoma.

  2015cited by this paper
• New Insights about Treg and Th17 Cells in HIV Infection and Disease Progression

  2015cited by this paper
• A dynamical model of the adaptive immune system: effects of cells promiscuity, antigens and B–B interactions

  2015cited by this paper
• CD4/CD8 ratio: an emerging biomarker for HIV.

  2015cited by this paper
• The ratio of Th17/Treg cells as a risk indicator in early acute respiratory distress syndrome

  2015cited by this paper
• Follicular regulatory T cells impair follicular T helper cells in HIV and SIV infection

  2015cited by this paper
• CD4:CD8 ratio as a frontier marker for clinical outcome, immune dysfunction and viral reservoir size in virologically suppressed HIV-positive patients

  2015cited by this paper
• Dynamics of B cells in germinal centres

  2015cited by this paper
• Fluctuating fitness shapes the clone-size distribution of immune repertoires

  2015cited by this paper
• Reconstructing a B-Cell Clonal Lineage. II. Mutation, Selection, and Affinity Maturation

  2014cited by this paper
• Associative networks with diluted patterns: dynamical analysis at low and medium load

  2014cited by this paper
• Agent-Based Modeling of the Immune System: NetLogo, a Promising Framework

  2014cited by this paper
• The CD4:CD8 ratio is associated with markers of age‐associated disease in virally suppressed HIV‐infected patients with immunological recovery

  2014cited by this paper
• HIV-Infected Individuals with Low CD4/CD8 Ratio despite Effective Antiretroviral Therapy Exhibit Altered T Cell Subsets, Heightened CD8+ T Cell Activation, and Increased Risk of Non-AIDS Morbidity and Mortality

  2014cited by this paper
• Long-term antiretroviral therapy initiated during primary HIV-1 infection is key to achieving both low HIV reservoirs and normal T cell counts.

  2013cited by this paper
• Regulatory T cells and B cells: implication on autoimmune diseases.

  2013cited by this paper
• Bayesian multivariate Poisson abundance models for T-cell receptor data.

  2013cited by this paper
• The Ratios of CD8+ T Cells to CD4+CD25+ FOXP3+ and FOXP3- T Cells Correlate with Poor Clinical Outcome in Human Serous Ovarian Cancer

  2013cited by this paper
• Do Natural T Regulatory Cells become Activated to Antigen Specific T Regulatory Cells in Transplantation and in Autoimmunity?

  2013cited by this paper
• Regulatory T Cells and the Immune Aging Process: A Mini-Review

  2013cited by this paper
• Antiretroviral therapy initiated within 6 months of HIV infection is associated with lower T-cell activation and smaller HIV reservoir size.

  2013cited by this paper
• Regulatory T cells use programmed death 1 ligands to directly suppress autoreactive B cells in vivo

  2012cited by this paper
• The inverted CD4/CD8 ratio and associated parameters in 66-year-old individuals: the Swedish HEXA immune study

  2012cited by this paper
• Subcellular localization of FOXP3 in human regulatory and nonregulatory T cells

  2012cited by this paper
• Loss of balance between T helper type 17 and regulatory T cells in chronic human immunodeficiency virus infection

  2011cited by this paper
• A thermodynamic perspective of immune capabilities.

  2011cited by this paper
• Self-tolerance and Autoimmunity in a Regulatory T Cell Model

  2011cited by this paper
• On the composition of the preimmune repertoire of T cells specific for Peptide-major histocompatibility complex ligands.

  2010cited by this paper
• Discrimination of membrane antigen affinity by B cells requires dominance of kinetic proofreading over serial triggering (112.10)

  2010cited by this paper
• Stochastic dynamics for idiotypic immune networks

  2010cited by this paper
• Nature Communications

  2010cited by this paper
• Nonlinear problem of active sound control

  2010cited by this paper
• A reversed CD4/CD8 ratio of tumor-infiltrating lymphocytes and a high percentage of CD4+FOXP3+ regulatory T cells are significantly associated with clinical outcome in squamous cell carcinoma of the cervix

  2010cited by this paper
• Agent‐based simulation of T‐cell activation and proliferation within a lymph node

  2010cited by this paper
• B-cell diversity decreases in old age and is correlated with poor health status

  2009cited by this paper
• Precise determination of the diversity of a combinatorial antibody library gives insight into the human immunoglobulin repertoire

  2009cited by this paper
• Cutting Edge: Regulatory T Cells Directly Suppress B Cells in Systemic Lupus Erythematosus1

  2009cited by this paper
• Taking Advantage: High-Affinity B Cells in the Germinal Center Have Lower Death Rates, but Similar Rates of Division, Compared to Low-Affinity Cells1

  2009cited by this paper
• Regulatory T cells: how do they suppress immune responses?

  2009cited by this paper
• How do Regulatory T Cells Work?

  2009cited by this paper
• Maximum entropy models for antibody diversity

  2009cited by this paper
• A Population Dynamics Analysis of the Interaction between Adaptive Regulatory T Cells and Antigen Presenting Cells

  2008cited by this paper
• How regulatory T cells work

  2008cited by this paper
• Immune activation and inflammation in HIV‐1 infection: causes and consequences

  2008cited by this paper
• The immune risk profile is associated with age and gender: findings from three Swedish population studies of individuals 20–100 years of age

  2008cited by this paper
• T-helper/T-regulator lymphocyte ratio as a new immunobiological index to quantify the anticancer immune status in cancer patients.

  2008cited by this paper
• Et al

  2008cited by this paper
• Regulatory T Cells Prevent CD8 T Cell Maturation by Inhibiting CD4 Th Cells at Tumor Sites1

  2007cited by this paper
• When three is not a crowd: a Crossregulation Model of the dynamics and repertoire selection of regulatory CD4+ T cells

  2007cited by this paper
• Modeling regulation mechanisms in the immune system.

  2007cited by this paper
• Removal kinetics of exchange transfusion.

  2007cited by this paper
• A Mathematical Model for Neutrophil Gradient Sensing and Polarization

  2007cited by this paper
• An analysis of B cell selection mechanisms in germinal centers.

  2006cited by this paper
• High Epitope Expression Levels Increase Competition between T Cells

  2006cited by this paper
• Regulatory T cell adjustment of quorum growth thresholds and the control of local immune responses.

  2006cited by this paper
• Activated CD4+CD25+ T cells selectively kill B lymphocytes.

  2006cited by this paper
• Influence of cultivation temperature on the ligninolytic activity of selected fungal strains

  2006cited by this paper
• Agent-based modeling of the context dependency in T cell recognition.

  2005cited by this paper
• Immunological self-tolerance: lessons from mathematical modeling

  2005cited by this paper
• Cutting Edge: Direct Suppression of B Cells by CD4+CD25+ Regulatory T Cells1

  2005cited by this paper
• Regional anaesthesia

  2003cited by this paper
• Immunity

  2003cited by this paper
• Models of CD8+ responses: 1. What is the antigen-independent proliferation program.

  2003cited by this paper
• Tolerance and immunity in a mathematical model of T-cell mediated suppression.

  2003cited by this paper
• Dynamics of Major Histocompatibility Complex Class II Compartments during B Cell Receptor–mediated Cell Activation

  2002cited by this paper
• Homeostatic control of lymphocyte survival: potential origins and implications

  2002cited by this paper
• Relationship between the size of the human immunodeficiency virus type 1 (HIV-1) reservoir in peripheral blood CD4+ T cells and CD4+:CD8+ T cell ratios in aviremic HIV-1-infected individuals receiving long-term highly active antiretroviral therapy.

  2002cited by this paper
• Life and death within germinal centres: a double‐edged sword

  2002cited by this paper
• Virus Dynamics: Mathematical Principles of Immunology and Virology

  2001influential reference
• Basic Immunology : Functions and Disorders of the Immune System

  2001cited by this paper
• The Dynamics of Human Cytomegalovirus Replication in Vivo

  1999cited by this paper
• Relationship between CD4+/CD8+ T cell ratio and T cell activation in systemic lupus erythematosus.

  1999cited by this paper
• Immunol. Cell Biol.

  1995cited by this paper
• Immunologic self-tolerance maintained by activated T cells expressing IL-2 receptor alpha-chains (CD25). Breakdown of a single mechanism of self-tolerance causes various autoimmune diseases.

  1995cited by this paper
• Cyclic re-entry of germinal center B cells and the efficiency of affinity maturation.

  1993cited by this paper
• Disease severity in rheumatoid arthritis: Relationships of plasma tumor necrosis factor-α, soluble interleukin 2-receptor, soluble CD4/CD8 ratio, neopterin, and fibrin D-dimer to traditional severity and functional measures

  1992cited by this paper
• The immune system in health and disease.

  1992cited by this paper
• Explanatory style and cell-mediated immunity in elderly men and women.

  1991cited by this paper
• Analysis of T helper and suppressor lymphocyte subsets in relation to the clinical stage of solid neoplasms.

  1990cited by this paper
• Specific unresponsiveness in rats with prolonged cardiac allograft survival after treatment with cyclosporine. III. Further characterization of the CD4+ suppressor cell and its mechanisms of action

  1990cited by this paper
• A simple model for the immune network.

  1990cited by this paper
• Persistent reduction of CD4/CD8 lymphocyte ratio amd cell activation before the onset of Type 1 (insulin-dependent) diabetes

  1989cited by this paper
• Image evolution in Hopfield networks.

  1988cited by this paper
• The B-cell clonotype repertoire.

  1978cited by this paper
• Exact Stochastic Simulation of Coupled Chemical Reactions

  1977cited by this paper
• Interface Focus

  year unknowncited by this paper

• Modelling the interplay between the CD4\documentclass[12pt]{minimal} \usepackage{amsmath} \usepackage{wasysym} \usepackage{amsfonts} \usepackage{amssymb} \usepackage{amsbsy} \usepackage{mathrsfs} \usepackage{upgreek} \setlength{\oddsidemargin}{-69pt} \begin{document}$$^{+}$$\end{document}+/CD8\docum

  2020cites this paper