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Published on: October 16, 2009
Human Soluble CD80 is generated by alternative splicing, and recombinant soluble CD80 binds to CD28 and CD152
M Kakoulidou1, R Giscombe, X Zhao
1Immunological Research Unit, Department of Medicine, Center for Molecular Medicine L8: 00, Karolinska Institutet, Karolinska Hospital, Stockholm, Sweden.
Insights
Soluble CD80 (sCD80) is present in 24% of healthy individuals. This soluble costimulatory factor can inhibit T-cell activation, suggesting potential therapeutic applications for T-cell-related diseases.
Area of Science:
- Immunology
- Molecular Biology
Background:
- CD80 is a key costimulatory factor primarily found on activated immune cells like monocytes, B cells, and dendritic cells.
- The existence and function of soluble forms of CD80 (sCD80) in human serum were previously unclear.
Purpose of the Study:
- To investigate the presence and characteristics of soluble CD80 (sCD80) in human serum.
- To determine the functional relevance and potential immunomodulatory effects of sCD80.
Main Methods:
- Detection and quantification of sCD80 in healthy individuals' serum.
- Identification and characterization of different sCD80 mRNA splice variants (s1CD80 and s2CD80) in various immune cells.
- Assessment of recombinant s1CD80 binding to other immune molecules and T cells.
- Evaluation of the immunomodulatory effects of recombinant sCD80 on T-cell responses in vitro.
Main Results:
- Soluble CD80 (sCD80) was detected in the serum of 24% of healthy individuals, with concentrations ranging from 0 to 1 mg/l.
- Two distinct mRNA splice variants, s1CD80 and s2CD80, were identified in different immune cell populations, differing in their structural domains.
- Recombinant s1CD80 demonstrated binding to CD152-Ig, CD28-Ig, and T cells, particularly activated T cells.
- Recombinant sCD80 exhibited immunomodulatory effects, inhibiting the mixed lymphocyte reaction and T-cell proliferation.
Conclusions:
- Soluble CD80 (sCD80) represents a novel soluble costimulatory factor found in human serum.
- sCD80 possesses functional activity, including the inhibition of T-cell activation.
- The findings suggest a potential therapeutic role for sCD80 in treating diseases characterized by T-cell hyperactivation.
Abstract:
CD80 is a costimulatory factor mainly expressed on the surface of activated monocytes, B cells and dendritic cells. In this study, we demonstrate that 24% of healthy individuals have soluble forms of CD80, sCD80, in their serum. The concentration of sCD80 ranged from 0 to 1 mg/l. At the mRNA level, we detected a spliced form s1CD80 (771 bp), in unstimulated monocytes and B cells, while another form named s2CD80 (489 bp) was expressed in activated T cells as well as in freshly isolated and activated monocytes. s1CD80 lacks the transmembrane domain, and the IgC-like domain plus the transmembrane domain are spliced out of s2CD80. We also present data demonstrating that recombinant s1CD80 binds to recombinant CD152-Ig and CD28-Ig. It can also bind to T cells, preferentially to activated T cells. Recombinant sCD80 had immunomodulatory effects shown by its inhibition of the mixed lymphocyte reaction and inhibition of T-cell proliferation. sCD80 in human serum adds a new member to the family of soluble receptors, implying a network of soluble costimulatory factors with functional relevance. The inhibitory effect of the recombinant protein on T-cell activation makes it a possible candidate for treatment of diseases associated with hyperactivated T cells.
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