期刊
JOURNAL OF IMMUNOLOGY
卷 193, 期 2, 页码 889-900出版社
AMER ASSOC IMMUNOLOGISTS
DOI: 10.4049/jimmunol.1303389
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资金
- Wellcome Trust [091157]
- Juvenile Diabetes Research Foundation International [9-2011-253]
- National Institute for Health Research Cambridge Biomedical Research Centre, Juvenile Diabetes Research Foundation International, Centre for Diabetes-Genes, Autoimmunity, and Prevention [4-2007-1003]
- National Institute of Allergy and Infectious Diseases [P01AI039671]
- Wellcome Trust Strategic Award [100140]
- National Institute for Health Research [NF-SI-0508-10275, NF-SI-0513-10143] Funding Source: researchfish
Expression of the CTLA-4 gene is absolutely required for immune homeostasis, but aspects of its molecular nature remain undefined. In particular, the characterization of the soluble CTLA-4 (sCTLA-4) protein isoform generated by an alternatively spliced mRNA of CTLA-4 lacking transmembrane-encoding exon 3 has been hindered by the difficulty in distinguishing it from the transmembrane isoform of CTLA-4, Tm-CTLA-4. In the current study, sCTLA-4 has been analyzed using novel mAbs and polyclonal Abs specific for its unique C-terminal amino acid sequence. We demonstrate that the sCTLA-4 protein is secreted at low levels following the activation of primary human CD4(+) T cells and is increased only rarely in the serum of autoimmune patients. Unexpectedly, during our studies aimed to define the kinetics of sCTLA-4 produced by activated human CD4(+) T cells, we discovered that Tm-CTLA-4 is associated with microvesicles produced by the activated cells. The functional roles of sCTLA-4 and microvesicle-associated Tm-CTLA-4 warrant further investigation, especially as they relate to the multiple mechanisms of action described for the more commonly studied cell-associated Tm-CTLA-4.
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