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Published on: May 31, 2018
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.
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.
Abstract:
CD2-CD48 interactions enhance T cell receptor-driven mouse T lymphocyte activation. However, the mechanism is not well understood. Here we show that blockade of CD2-CD48 interactions with anti-CD48 monoclonal antibody (mAb) inhibited interleukin (IL)-2 and interferon (IFN)-gamma expression, as well as T cell proliferation in response to mitogenic anti-CD3 mAb, although more potent inhibition resulted from blocking CD28-CD80/CD86 interactions. Blockade of both CD2 and CD28 costimulation abrogated T cell proliferation and cytokine synthesis. Conversely, T cells stimulated with immobilized anti-CD3 and anti-CD2 mAb exhibited increased proliferation and IL-2 and IFN-gamma expression, although a stronger enhancing effect was obtained with immobilized anti-CD3 and anti-CD28 mAb. Concurrent CD2 and CD28 costimulation caused a further increase in proliferation and cytokine synthesis. Stimulation of purified T cells with microsphere-immobilized anti-CD3 and anti-CD2 mAb increased IL-2 and IFN-gamma mRNA stability. However, CD28 costimulation had a stronger enhancing effect on IL-2 and IFN-gamma mRNA stability that was not further increased by concomitant CD2 signaling. CD2, therefore, costimulates T cell activation by stabilizing cytokine mRNA transcripts, albeit with less efficiency than CD28.
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