title: IL-4 and IL-2 promote human T-cell proliferation through symmetrical but independent pathways.
abstract: The role of IL-4 and IL-2 on normal human T-cell activation and proliferation was studied. Both IL-2 and IL-4 were unable to induce proliferation of resting T cells. Therefore, we investigated their effect and the regulation of the T-cell proliferative response in competent T cells. T cells were rendered competent following incubation with PDB/ionomycin for 30 min or suboptimal concentrations of PHA for 60 min. Cells were then washed and recultured with PDB, IL-2, or IL-4 in the second or progression phase of the culture. Cells cultured in medium alone in this phase did not proliferate. IL-2 and IL-4 independently promoted competent T cells to proliferate to a similar degree as the response to PDB and the combination of IL-2 and IL-4 was not additive. The induction of competence and subsequent responsiveness to IL-2 and IL-4 could be maintained for about 24 hr after which time they become gradually less responsive to the interleukin in the progression phase. Addition of anti-IL-2R mAb or anti-IL-2 mAb resulted in selective inhibition of IL-2-mediated proliferation only. Similarly, addition of anti-IL-4 mAb resulted only in inhibition of IL-4-mediated proliferation. Addition of IL-2 during the progression phase led to an enhancement of IL-2R (TAC) expression while IL-4 did not affect IL-2R expression. The production of IL-2 and IL-4 by competent T cells could not be enhanced by the noncorresponding lymphokine. These results on the protein level were confirmed at the mRNA level as well and demonstrated that only PDB and IL-2 could induce IL-2 mRNA and PDB and IL-4 enhanced IL-4 mRNA. The immunosuppressive drug, cyclosporin A, failed to inhibit progression triggered by PDB, IL-2 or IL-4 in competent T cells. These findings suggest that IL-2 and IL-4 trigger T-cell proliferation through symmetrical, but independent pathways.
authors.affiliation: Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado.
authors.forename: R
authors.initials: R
authors.lastname: Or
authors.forename: H
authors.initials: H
authors.lastname: Renz
authors.forename: N
authors.initials: N
authors.lastname: Terada
authors.forename: E W
authors.initials: EW
authors.lastname: Gelfand
mesh_terms: D000906:Antibodies / Q000502:physiology; D001483:Base Sequence; D016572:Cyclosporine / Q000494:pharmacology; D004247:DNA / Q000096:biosynthesis; D006801:Humans; D007121:Immunocompetence / Q000187:drug effects; D007376:Interleukin-2 / Q000502:physiology*; D015847:Interleukin-4 / Q000276:immunology / Q000502:physiology*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000502:physiology; D008969:Molecular Sequence Data; D015375:Receptors, Interleukin-2 / Q000276:immunology / Q000502:physiology; D013601:T-Lymphocytes / Q000276:immunology*
chemical_list: D000906:Antibodies; D007376:Interleukin-2; D015375:Receptors, Interleukin-2; D015847:Interleukin-4; D016572:Cyclosporine; D004247:DNA