To the Editor: Interleukin-7 (IL-7) is an essential cytokine that is in constant production by nonhematopoietic cells. One of its roles is to control thymopoiesis and the homeostasis of peripheral T lymphocytes. It also stimulates T-cell immune functions. It acts through a receptor that is composed of 2 chains: IL-7Ralpha or CD127 and gamma c or CD132. 1 IL-7 plasma levels are increased in HIV-infected patients and this would seem to be related to the CD4 lymphopenia that gradually appears during the chronic phase of the disease. 2 IL-7 levels are also elevated in other lymphopenic conditions, for example, chemotherapyinduced lymphopenia, acute lymphocytic leukemia, idiopathic lymphopenia, etc. 3, 4 The precise mechanism leading to this increase in IL-7 is unknown. Recently, sCD127 was detected by Western blotting in human plasma. 5 We have confirmed and extended this finding by means of an enzyme-linked immunosorbent assay (ELISA) developed in our laboratory. Plasma samples are incubated in plates coated with goat anti-CD127 antibodies, bound sCD127 is detected by anti-CD127 monoclonal antibody (mAb) 40 131, biotinylated anti-mouse immunoglobulin, and streptavidin horse radish peroxidase (HRP). Recombinant human CD127-Fc chimera protein is used as a standard. All the reagents used in this study were obtained from R & D Systems, Minneapolis, MN. This ELISA technique was used to show that plasma sCD127 is far more abundant (23.6 G 3.5 ng/mL, n= 20) than IL-7, which is found to be in the picogram range. 6 A full characterization of the sCD127 molecules will be reported later. We tested sCD127 interference on IL-7 and here discuss the putative consequences of our findings with regard to the mechanism that increases IL-7 in the plasma of HIV-positive patients and the function of the IL-7/IL-7 receptor system. We first determined the proportion of IL-7 bound to sCD127 in plasma samples taken from healthy individuals. Plasma (n= 6) were adsorbed onto rabbit anti-CD127 polyclonal antibodies coated on agarose beads. Rabbit polyclonal immunoglobulin-coated beads were used as a control. As seen in Figure 1A, most of the sCD127 molecules were specifically removed from the plasma by the anti-CD127 beads. An assay was then conducted on the same untreated or adsorbed plasma samples to determine their IL-7 content. A significant fraction of the IL-7 was seen to be bound to sCD127, thus indicating that IL-7 has affinity for sCD127. In view of this result, we tested the putative interference caused by sCD127-containing plasma on the assay of IL-7 (Quantikine HS, Human IL-7 & Immunoassay). Before the assay, the IL-7 was diluted either in the control solution provided by the supplier or in this same solution containing 0.5% plasma. As can be seen in Figure 1B, the amount of IL-7 detected was unaffected by the presence of sCD127 derived from the plasma of healthy individuals, even at very low IL-7 concentrations. This suggests that the affinity of the anti–IL-7 antibodies used in the assay is far higher than that of IL-7 for sCD127. More significantly, the results indicate that changes in the quantity of sCD127 in the plasma do not affect the assay of IL-7. We then compared IL-7 affinity for membrane-expressed CD127 with its affinity for plasma sCD127. CD127 is constitutively and highly expressed at the surface of resting CD4 T lymphocytes, whereas gamma c expression is low or undetectable. Most CD127 molecules are therefore free. The study was performed with allophycocyanin-labeled anti-CD4 mAb used to stain CD4 T lymphocytes from peripheral blood mononuclear cell. Two CD127-specific …