Steinberger I, Ben-Bassat H, Hochberg E, Lorberboum-Galski H. Interleukin-2 (IL-2) Receptor a, b and g Subunit Expression as a Function of B-Cell Lineage Ontogeny: the Use of IL-2-PE66 4Glu to Characterize Internalization via IL-2 Receptor Subunits. Scand J Immunol 1997;46:129-136 Interleukin-2 (IL-2) is a pluripotent cytokine which plays a crucial role in the immune system response. Although the IL-2/IL-2 receptor (IL-2R) system has been well characterized in cells of the T lineage it is less known in B lymphocytes. The authors therefore studied the expression of the IL-2Ra, b and g subunits in human B-cell lines at different stages of maturation, by the polymerase chain reaction technique. The authors found that the a and b subunits are expressed in the final stages of B-cell lineage maturation, whereas the g subunit is constitutively expressed during B-lymphocyte differentiation. The results indicate that the IL-2/ IL-2R system, most probably, does not have a role in the early stages of B-cell differentiation, but may be involved only in the final stages of B-cell lineage ontogeny. Moreover, the ability of the different forms of IL-2R to internalize the IL-2 ligand was investigated, using the chimeric protein IL-2-PE66 4Glu . Cell lines bearing the ag, bg and abg forms of IL-2R were inhibited by the chimeric protein, while those bearing the g subunit alone did not respond to the chimera. Thus, internalization of IL-2 is most likely mediated via the ag form of the IL-2R, as shown here for the first time, as well as through the bg and abg IL-2R forms. However, IL-2 cannot be internalized through the IL-2R g subunit alone.

A construct of IL-2 and pseudomonas exotoxin (PE40) has been genetically engineered. An aliquot of 100 microliter of the chimeric protein, radiolabelled with I125, was administered to healthy rats by various routes. At different intervals, ocular and non ocular tissues were removed and the levels of the radiolabelled chimeric protein IL-2-PE40 measured. Systemic administration of IL2-PE40 either intravenously (IV) or intraperitoneally (IP) leads to high levels of the drug in the blood, liver and spleen. Little or no radioactivity is observed within the ocular tissues using this route. On the other hand, local administration of the drug either as subtenon injection or as eye drops resulted in a very high concentration of the drug within the conjunctiva, cornea and sclera, with little radioactivity detected systemically. Subtenon injection induced a significant drug level within the optic nerve. With the drops, the chimeric protein was also detected, in low levels, intraocularly.