Figure 2.

CD46–IL-2 signals induce a switch from a T_H1 phenotype to a suppressive Tr1 phenotype in CD4⁺ T cells. (a) Flow cytometry of the induction of IL-10-secreting T cells by anti-CD46 from an initial T_H1 effector cell (1) or from a distinct cell subset (2). (b) T_H1 lineage induction in purified CD4⁺ T cells left not activated or activated with anti-CD3 and anti-CD46 plus IL-2 (50 U/ml IL-2) and isotype-matched control antibody or neutralizing mAb to IFN-γ or IL-10, presented as the percentage of cytokine-positive (Cyt⁺) cells: IFN-γ⁺IL-10⁻, IFN-γ⁺IL-10⁺ or IFN-γ⁻IL-10⁺ (key). *P < 0.05 and **P < 0.01 (Student’s t-test). Data are representative of three experiments (mean ± s.d.). (c) Secretion of IFN-γ and IL-10 by IFN-γ⁺IL-10⁻ cells isolated by flow cytometry from purified T cells activated for 36 h (primary stimulation (1°)) with anti-CD3 alone or with anti-CD3 and anti-CD46 in the presence of IL-2 (5 U/ml); the IFN-γ⁺IL-10⁻ populations were expanded for 4 d with IL-2 (5 U/ml), then restimulated (above plots; secondary stimulation (2°)) and assayed 18 h later. Numbers in plots indicate percent IFN-γ⁺IL-10⁻ cells (top left), IFN-γ⁺IL-10⁺ cells (top right) or IFN-γ⁻IL-10⁺ cells (bottom right). Data are representative of four experiments.