Circulating Interleukin-2 Receptors Are a Group of Multimeric Proteins with Immunoreactivity for Interleukin-2 Receptor α, β, and γ Chains

Abstract

Soluble interleukin-2 receptor (sIL-2R) alpha chain serum levels as determined by enzyme-linked immunosorbant assay (ELISA) are commonly used to monitor various inflammatory and neoplastic disorders associated with lymphocytic proliferation and activation. The in vivo structure of this soluble receptor species, however, is not characterized. We investigated sera with elevated sIL-2R serum levels of patients with histologically proven cutaneous T cell lymphoma (CTCL) and high-dose IL-2-treated melanoma patients and healthy donors. Purified recombinant IL-2R alpha and beta chain molecules, produced by transfection of NIH/3T3 fibroblasts and CHO cells, served as positive controls for purification and detection procedures. For selective enrichment of IL-2R molecules from supernatants and sera, affinity columns were prepared by coupling recombinant IL-2 or monoclonal antibodies against the alpha and the beta chain of the IL-2R complex to cyanogen bromide-activated Sepharose. Western blotting with affinity-purified fractions under reducing and nonreducing conditions revealed proteins that showed immunoreactivity for IL-2R alpha, beta, and gamma chain using several detection antibodies against these molecules. We conclude that the composition of sIL-2R in vivo is more complex than that of recombinant sIL-2R and can include all three IL-2R chains.

Soluble IL-2Rα (sCD25) Exacerbates Autoimmunity and Enhances the Development of Th17 Responses in Mice

“…Similar to other cytokine receptors expressed at the cell surface, the individual chains of the IL-2R are also known to exist in soluble form in serum [21], [22]. In particular, stable expression levels of soluble CD25 observed in healthy adults has underscored its clinical use as a biomarker for a variety of inflammatory conditions [23].…”

Serological Immunomarkers in Cutaneous T Cell Lymphoma

“…It can be secreted directly or by shedding from the cell surface [12]. In vivo multimeric soluble complexes including the IL-2R β- and γ-chains are circulating in the serum [13]. In neoplastic diseases (mainly lymphomas), size could be correlated to tumor burden, therapy responsiveness and prognosis for NHL [14].…”

Orf Virus Encodes a Novel Secreted Protein Inhibitor of Granulocyte-Macrophage Colony-Stimulating Factor and Interleukin-2

“…The ovIL-2R ␣ chain has been cloned and sequenced (5), but there are no regions of homology between this sequence and GIF. There is a natural secreted form of the IL-2R ␣ subunit and evidence of secreted forms of the IL-2R ␤ and ␥ subunits (11,30). All of these subunits have a low affinity for IL-2.…”