Unstimulated peripheral blood mononuclear cells from patients with angiocentric T cell
immunoproliferative disorders and
concanavalin A-stimulated normal peripheral blood mononuclear cells secrete a phagocytosis-inducing factor (PIF) that induces a fivefold to 50-fold enhancement of phagocytosis of
IgG-coated ox red blood cells by U937 cells. We investigated the identity, production, and mechanism of the action of PIF. PIF activity was demonstrated in supernatants from nine of 44
phytohemagglutinin-stimulated
interleukin 2 (IL 2)-dependent T cell lines and clones derived from purified T4+ cells, but was not found in supernatants from 26 lines and clones derived from
phytohemagglutinin-stimulated T8+ cells. In addition, PIF was produced by four of four
antigen-specific T cell lines and clones after stimulation with the appropriate
antigen and antigen-presenting cells, and by HUT-102, a human T cell lymphotropic virus type I-transformed T cell line. PIF from all of these sources caused significant inhibition of U937 proliferation. This proliferation-inhibiting activity co-purified with phagocytosis-enhancing activity in sizing procedures and isoelectric focusing, which yielded an estimated m.w. of 35,000 to 55,000 and an estimated isoelectric point of 5.0 to 6.0 for PIF. In contrast, IL 2, recombinant
interferon-alpha, and recombinant
interferon-gamma had no effect on phagocytosis by U937 cells, and
antibodies to
interferon-alpha and
interferon-gamma did not block the phagocytosis-inducing activity of PIF-containing supernatants. PIF appears to be a distinct lymphokine produced by a subset of T4+ lymphocytes, possibly those that proliferate in response to
antigen. PIF may be important in the induction of erythrophagocytosis, which is associated with certain T cell
immunoproliferative disorders.