CD2-CD48 interactions promote interleukin-2 and interferon-gamma synthesis by stabilizing cytokine mRNA

Bruce L Musgrave1, Carrie L Watson, S M Mansour Haeryfar

  • 1Department of Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 1X5, Canada.

Cellular Immunology
|August 28, 2004
PubMed

Insights

CD2-CD48 interactions boost T lymphocyte activation by stabilizing cytokine mRNA. While CD2 costimulation enhances T cell responses, CD28 signaling demonstrates a more potent effect on cytokine mRNA stability and T cell proliferation.

Area of Science:

  • Immunology
  • Cellular Biology

Background:

  • CD2-CD48 interactions are known to enhance T cell receptor-driven T lymphocyte activation.
  • The precise mechanisms underlying CD2-mediated costimulation remain incompletely understood.

Purpose of the Study:

  • To elucidate the role of CD2-CD48 interactions in T lymphocyte activation.
  • To compare the costimulatory effects of CD2 and CD28 pathways on T cell responses.

Main Methods:

  • Utilized anti-CD48 monoclonal antibody (mAb) to block CD2-CD48 interactions.
  • Assessed T cell proliferation and cytokine (IL-2, IFN-gamma) expression following stimulation with anti-CD3 mAb.
  • Investigated the impact of blocking CD2 and CD28 costimulatory pathways.
  • Examined mRNA stability of IL-2 and IFN-gamma upon stimulation with immobilized anti-CD3 and anti-CD2 or anti-CD3 and anti-CD28 mAb.

Main Results:

  • Blockade of CD2-CD48 interactions inhibited IL-2 and IFN-gamma expression and T cell proliferation.
  • Blocking both CD2 and CD28 costimulation abrogated T cell activation.
  • Stimulation with anti-CD3 and anti-CD2 mAb increased proliferation and cytokine expression, with CD28 providing a stronger enhancement.
  • CD2 costimulation stabilized IL-2 and IFN-gamma mRNA, but CD28 exhibited a more pronounced effect.

Conclusions:

  • CD2 costimulates T cell activation, partly by enhancing the stability of cytokine mRNA transcripts.
  • CD28 costimulation is more potent than CD2 in stabilizing cytokine mRNA and promoting T cell activation.
  • Combined CD2 and CD28 signaling leads to additive increases in T cell proliferation and cytokine synthesis.

Related Concept Videos

Inhibition of Cdk Activity02:34

Inhibition of Cdk Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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...
Inhibition of CDK Activity02:34

Inhibition of CDK Activity

The orderly progression of the cell cycle depends on the activation of Cdk protein by binding to its cyclin partner. However, the cell cycle must be restricted when undergoing abnormal changes. Most cancers correlate to the deregulated cell cycle, and since Cdks are a central component of the cell cycle, Cdk inhibitors are extensively studied to develop anticancer agents. For instance, cyclin D associates with several Cdks, such as Cdk 4/6, to form an active complex. The cyclin D-Cdk4/6 complex...
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...
Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...