Related Experiment Video

Updated: Aug 10, 2026

Assessing the Innate Sensing of HIV-1 Infected CD4+ T Cells by Plasmacytoid Dendritic Cells Using an Ex vivo Co-culture System.
08:11

Assessing the Innate Sensing of HIV-1 Infected CD4+ T Cells by Plasmacytoid Dendritic Cells Using an Ex vivo Co-culture System.

Published on: September 1, 2015

Cytokines regulate expression and function of the HIV coreceptor CXCR4 on human mature dendritic cells

J P Zoeteweij1, H Golding, H Mostowski

  • 1Dermatology Branch, National Cancer Institute, Bethesda, MD 20892, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|October 6, 1998
PubMed

Insights

Cytokine dysregulation influences HIV-1 spread. Interleukin-4 (IL-4) and transforming growth factor-beta1 (TGF-beta1) increase CXCR4 on dendritic cells (DCs), promoting T-cell-tropic HIV infection. Interferons decrease CXCR4, reducing infection.

Area of Science:

  • Immunology
  • Virology
  • Cell Biology

Background:

  • Dendritic cells (DCs) are crucial in HIV-1 transmission to CD4+ T cells.
  • Cytokine profiles can shift during HIV disease progression.
  • Understanding DC-HIV interactions is key to controlling viral spread.

Purpose of the Study:

  • To investigate how cytokines regulate HIV coreceptors on mature dendritic cells (cultured Langerhans cells, cLC).
  • To determine the impact of CXCR4 and CCR5 expression on HIV infection levels.

Main Methods:

  • Cultured Langerhans cells (cLC) were treated with various cytokines (IL-4, TGF-beta1, IFN-alpha, IFN-beta, IFN-gamma).
  • Cell surface expression of CXCR4 and CCR5 on cLC was measured.
  • Syncytium formation and infection levels using T-cell-tropic (X4) HIV were assessed.

Main Results:

  • IL-4 and TGF-beta1 up-regulated CXCR4 expression on cLC.
  • IFN-alpha, IFN-beta, and IFN-gamma inhibited CXCR4 expression on cLC.
  • CCR5 expression was not significantly affected by the tested cytokines.
  • Increased CXCR4 expression correlated with enhanced X4-HIV envelope-mediated syncytium formation and infection.

Conclusions:

  • Cytokine modulation of CXCR4 on mature DCs impacts X4-HIV infectivity.
  • Shifts towards type 2 cytokine dominance in HIV disease may enhance CXCR4 expression, promoting X4-HIV infection.
  • Cytokine dysregulation is potentially linked to the emergence of X4-HIV strains during AIDS progression.

More Related Videos

Generation of Human Monocyte-derived Dendritic Cells from Whole Blood07:35

Generation of Human Monocyte-derived Dendritic Cells from Whole Blood

Published on: December 24, 2016

A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 406:56

A Flow Cytometry-based Assay to Identify Compounds That Disrupt Binding of Fluorescently-labeled CXC Chemokine Ligand 12 to CXC Chemokine Receptor 4

Published on: March 10, 2018

Related Concept Videos

Anaphase Promoting Complex00:50

Anaphase Promoting Complex

The stepwise destruction of specific proteins is necessary for the progression and completion of the cell cycle. Such proteins are ubiquitinated by ubiquitin ligases and then subsequently destroyed by the proteasome. The SCF (Skp1/Cullin/F-box) and the anaphase-promoting complex (APC) are two important ubiquitin ligases involved in cell cycle progression. While SCF is active throughout the cell cycle, APC gets activated during metaphase to anaphase transition. Cdc20 or Cdh1 binds to APC and...
Receptor Downregulation in MVBs01:15

Receptor Downregulation in MVBs

Multivesicular bodies (MVBs) are mature endosomes that sort ubiquitinated proteins and then fuse with lysosomes to degrade the sorted proteins. Epidermal growth factor (EGF) and its receptor (EGFR) form a complex that can be internalized through endocytosis, sorted into an MVB, and later degraded.
The EGFR can initiate signaling pathways that  lead to cell proliferation, migration, and differentiation. Overexpression of EGFR  stimulates cells to proliferate. Excessive  EGFR activation may...
The JAK-STAT Signaling Pathway01:20

The JAK-STAT Signaling Pathway

Several cytokine receptors have tightly bound Janus kinase or JAK proteins attached at their cytosolic tail. Small signaling molecules such as cytokines, growth hormones, or prolactins bind to the cytokine receptors and initiate their dimerization. The dimerization brings the cytosolic JAKs together that trans-phosphorylate and activates each other. The activated JAKs now phosphorylate cytosolic tails of the cytokine receptors, which serve as binding sites for adaptor proteins such as  SH2...
T Cell Activation and Clonal Selection01:22

T Cell Activation and Clonal Selection

T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
Naive T cells that have not yet encountered an antigen express two primary CD...
T Cell Types and Functions01:24

T Cell Types and Functions

When T cells with CD4 markers are activated, they give rise to two types of effector cells: helper T cells and regulatory T cells. Meanwhile, T cells with CD8 markers differentiate into effector cytotoxic T cells. The differentiation of CD4 T cells into helper T cell subsets, such as Th1, Th2, and Th17 cells, is dependent on the antigen type, antigen-presenting cell, and regulatory cytokines.
Th1 cells stimulate dendritic cells to express necessary co-stimulatory molecules on their surfaces for...
Cytotoxic T Cells-mediated Immune Response01:27

Cytotoxic T Cells-mediated Immune Response

Cytotoxic T cells are a vital component of the immune system. They have the remarkable ability to identify and target antigens on infected or abnormal cells. These antigens often originate from intracellular pathogens such as viruses or abnormal proteins cancer cells produce.
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...