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Published on: October 17, 2009
Soluble CD86 is a costimulatory molecule for human T lymphocytes
P Jeannin1, G Magistrelli, J P Aubry
1Centre d'Immunologie Pierre Fabre, Saint Julien en Genevois, France.
Insights
Soluble CD86, a functional costimulatory molecule, is found in human serum. It is produced by monocytes and can activate T cells, suggesting a role in immune surveillance.
Area of Science:
- Immunology
- Molecular Biology
Background:
- CD86 is a key costimulatory molecule essential for T cell activation.
- Its role in soluble form and its presence in human serum were previously uncharacterized.
Purpose of the Study:
- To investigate the presence and function of soluble CD86 in human serum.
- To characterize the molecular nature and biological activity of soluble CD86.
Main Methods:
- Detection of soluble CD86 in human serum.
- Analysis of alternatively spliced CD86 transcripts (CD86deltaTM).
- Recombinant CD86deltaTM binding assays with CD28 and CTLA-4.
- T cell activation assays using anti-CD3 mAb and Flu M1 peptide.
Main Results:
- Soluble CD86 was detected in human serum, originating from resting monocytes.
- An alternatively spliced transcript, CD86deltaTM, lacking the transmembrane domain, was identified as the source.
- Recombinant CD86deltaTM demonstrated binding to CD28 and CTLA-4.
- Soluble CD86 induced T cell activation and IFNgamma production in virus-specific memory T cells.
Conclusions:
- Soluble CD86 is a biologically active molecule present in human serum at functional concentrations.
- This soluble form of CD86 may play a significant role in immune surveillance.
Abstract:
CD86 is an important costimulatory molecule for the priming and activation of naive and memory T cells, respectively. Here, we show that soluble CD86 is detected in human serum. Soluble CD86 is produced by resting monocytes and results from an alternatively spliced transcript (CD86deltaTM) characterized by deletion of the transmembrane domain. Recombinant CD86deltaTM binds to CD28 and CTLA-4 and induces the activation of T cells after stimulation with anti-CD3 mAb. CD86deltaTM also induces IFNgamma production by virus-specific CD8+ memory human T cells stimulated with the Flu M1 peptide. The concentrations of soluble CD86 found in human serum are sufficient to induce biological activity. Soluble CD86 molecule, therefore, appears to be a functional costimulatory molecule playing a potentially important role in immune surveillance.
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