Monoclonal antibody OKT11A inhibits and recombinant interleukin 2 (IL 2) augments expression of IL 2 receptors at a pretranslational level.
The expression of receptors for interleukin 2 (IL 2) represents a critical event regulating the growth of normal T lymphocytes. We investigated the effects of the inhibitory monoclonal antibody OKT11A (anti-sheep erythrocyte receptor) and of purified recombinant IL 2 (rIL 2) on the expression of IL 2 receptors by activated T cells at both the protein and the mRNA levels. Adding OKT11A antibody (0.5 microgram/ml) to phytohemagglutinin (PHA)-stimulated cultures of human peripheral blood mononuclear cells (PBMC) markedly suppressed cellular proliferation (assessed by [3H]thymidine incorporation) and IL 2 receptor expression (determined by immunofluorescence assay by using the anti-IL 2-receptor antibody, anti-Tac). Northern blot analysis performed with the use of a cDNA probe specific for the human IL 2 receptor gene demonstrated that OKT11A antibody also decreased the accumulation of IL 2 receptor mRNA induced by PHA in PBMC. Purified rIL 2 (10 U/ml) alone had little effect on the expression of IL 2 receptors in unstimulated PBMC cultures. In combination with PHA or with PHA plus OKT11A, however, rIL 2 augmented both the expression of IL 2 receptor protein on PBMC and the accumulation of IL 2 receptor mRNA in PBMC. Adding anti-Tac antibody to PBMC cultures to block the interaction of IL 2 with its receptor diminished the accumulation of IL 2 receptor mRNA induced by PHA. Taken together, these data demonstrate that OKT11A antibody inhibits and IL 2 augments expression of IL 2 receptors on PHA-stimulated T cells, at least in part, at a pretranslational level.
D000276:Adjuvants, Immunologic / Q000502:physiology; D000911:Antibodies, Monoclonal / Q000502:physiology*; D001345:Autoradiography; D001667:Binding, Competitive; D004247:DNA / Q000096:biosynthesis; D005455:Fluorescent Antibody Technique; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics / Q000502:physiology*; D008213:Lymphocyte Activation; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000378:metabolism*; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D015375:Receptors, Interleukin-2; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D000276:Adjuvants, Immunologic; D000911:Antibodies, Monoclonal; D007376:Interleukin-2; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D015375:Receptors, Interleukin-2; D004247:DNA