Related Experiment Video

Updated: Aug 7, 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

Reciprocal desensitization of CCR5 and CD4 is mediated by IL-16 and macrophage-inflammatory protein-1 beta,

M V Mashikian1, T C Ryan, A Seman

  • 1Pulmonary Center, Boston University School of Medicine, MA 02118, USA.

Journal of Immunology (Baltimore, Md. : 1950)
|September 8, 1999
PubMed

Insights

Interleukin-16 (IL-16) signaling via CD4 selectively desensitizes the CCR5 receptor in T cells, inhibiting macrophage-inflammatory protein (MIP)-1 beta chemotaxis. This cross-desensitization is reciprocal and p56lck-dependent, revealing a selective interaction between CD4 and CCR5.

Area of Science:

  • Immunology
  • Cellular Signaling

Background:

  • HIV-1 gp120's inhibition of chemokine signaling suggests ligand-induced modulation of chemokine receptor function.
  • Understanding how natural ligands binding to CD4 affect T cell responses to chemokines is crucial.

Purpose of the Study:

  • To investigate if Interleukin-16 (IL-16) signaling through CD4 alters T cell responsiveness to chemokine stimulation.
  • To elucidate the mechanisms and selectivity of IL-16/CD4-mediated modulation of chemokine receptor function.

Main Methods:

  • Utilizing T lymphocytes and murine T cell hybridomas expressing CD4 variants.
  • Assessing chemotaxis in response to various chemokines (MIP-1 beta, MCP-2) and their receptors (CCR5, CCR1, CCR2, CCR3).
  • Investigating the role of p56lck kinase activity in IL-16 signaling and receptor desensitization.

Main Results:

  • IL-16/CD4 signaling selectively inhibits macrophage-inflammatory protein (MIP)-1 beta/CCR5-induced chemotaxis without affecting other chemokine pathways.
  • CCR5 desensitization by IL-16 requires 10 minutes of pretreatment and is p56lck-dependent, but does not alter receptor expression or MIP-1 beta binding.
  • The desensitization is reciprocal: CCR5 stimulation inhibits IL-16/CD4-induced migration, while CCR1, CCR2, or CCR3 stimulation does not.

Conclusions:

  • IL-16/CD4 signaling induces a selective, reciprocal cross-desensitization of the CCR5 receptor.
  • p56lck kinase activity is essential for CCR5 desensitization but not for IL-16-induced migration.
  • These findings reveal a selective cross-talk between CD4 and CCR5 mediated by inflammatory cytokines.

More Related Videos

Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes11:48

Isolation Protocol of Mouse Monocyte-derived Dendritic Cells and Their Subsequent In Vitro Activation with Tumor Immune Complexes

Published on: May 31, 2018

Isolation, Transfection, and Culture of Primary Human Monocytes09:13

Isolation, Transfection, and Culture of Primary Human Monocytes

Published on: December 16, 2019

Related Concept Videos

Cell-mediated Immune Responses01:40

Cell-mediated Immune Responses

Overview
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...
Immune Response Against Viral Pathogens01:29

Immune Response Against Viral Pathogens

The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
NK Cells
NK cells are a crucial part of our innate immune system, acting as the first line of defense against viral infections. These cells can recognize and kill infected cells without prior exposure to the virus, effectively slowing down the spread of infection. Additionally, NK cells produce proinflammatory...