Mechanisms by which accessory cells contribute in growth of resting T lymphocytes initiated by OKT3 antibody.

This study was undertaken to determine how accessory cells (AC) participate in growth of normal resting T cells initiated by anti-T3 monoclonal antibodies. Highly purified peripheral blood resting T cells were obtained by sequentially using three procedures (adherence to plastic surface, adherence to nylon wool columns and treatment with four monoclonal antibodies against antigens on AC and activated T cells plus complement). The assays for T cell growth were carried out at low cell density (10(4) cells/well) and with T cell populations where we could not detect cells bearing OKM1 and Ia antigens. Soluble OKT3 antibody, concanavalin A, recombinant interleukin 2 (IL 2) or purified interleukin 1 (IL 1) alone did not induce proliferation of purified resting T cells. Recombinant IL2 together with soluble OKT3 antibody stimulated significant growth whereas purified IL1 and two distinct preparations derived from AC containing IL 1 activity did not. Nevertheless, purified IL 1 amplified the proliferation of T cells induced by soluble OKT3 antibody in the presence of a small number of irradiated AC (3%). Phorbol myristate acetate (PMA) together with soluble OKT3 antibody activated purified resting T cells to proliferate, but PMA alone had little growth-promoting activity only. Soluble OKT3 antibody did not by itself induce a detectable number of resting T cells to express receptors for IL2 as determined by direct immunofluorescence staining and FACS analysis with monoclonal anti-IL2 receptor antibody. Cloned IL2 or purified IL1 alone did not induce resting normal T cells to express receptors for IL2 either. In contrast, T cells exposed to both soluble OKT3 antibody and IL2 exhibited IL2 receptors. PMA alone stimulated some resting T cells to express IL2 receptors and this response was significantly increased when the drug was used together with soluble OKT3 antibody. Studies were performed with unfractionated mononuclear cells from a donor whose cells respond to OKT3 (IgG2) but not to Leu 4 (IgG1) anti-T3 antibodies. Recombinant IL 2 but not purified IL 1 corrected the defective response to Leu 4 antibody. Finally, OKT3 antibody linked to beads, but not in soluble form, and purified IL1 replaced AC in growth of purified resting T cells. Based on these data I conclude the following: (a) AC participate in growth of resting normal T cells initiated by anti-T3 antibodies through their Fc receptors in two ways, namely, by providing a matrix to favour cross-linking of the T3 complex and simultaneously by secreting IL1.(ABSTRACT TRUNCATED AT 400 WORDS)