Identification and Biochemical Characterization of Human Plasma Soluble IL-7R: Lower Concentrations in HIV-1-Infected Patients

The IL-7R alpha-chain and the common gamma-chain (gamma(c)) are both components of IL-7R. Human plasma harbors soluble forms of IL-7R (sIL-7R alpha and s gamma(c)) that are detected and assayed by Western blotting, showing that the levels of sIL-7R alpha are higher than the levels of s gamma(c) (47.5 ng/ml and 1.5 ng/ml, respectively). Gel electrophoresis and tandem mass spectrometry used to analyze deglycosylated, affinity-purified protein showed that sIL-7R alpha is generated through differentially spliced mRNA, not by membrane receptor shedding. Plasma sIL-7R alpha and s gamma(c) are present as heterocomplexes and s gamma(c) was found to be mainly associated with sIL-7R alpha. The affinities of two IL-7 binding sites (K-d = 35 +/- 8 pM and K-d = 3 +/- 1 nM) were similar to that of the membrane receptor, suggesting that the sIL-7R alpha/s gamma(c) complex retains high affinity for IL-7. sIL-7R alpha mRNA is constitutively present among peripheral T lymphocytes and is down-modulated in vitro by IL-7. Chronically HIV-1-infected patients (n = 20) showed no significant (p > 0.714) variation in s gamma(c) levels and a significant (p < 0.0014) 2-fold decrease in plasma sIL-7R alpha levels compared with those in control healthy individuals. Plasma IL-7 and sIL-7R alpha levels did not show any obvious relationship. The Journal of Immunology, 2009, 182: 7389-7397.