Human T4+ lymphocytes produce a phagocytosis-inducing factor (PIF) distinct from interferon-alpha and interferon-gamma.
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.
J B
JB
Margolick
J L
JL
Ambrus
D J
DJ
Volkman
A S
AS
Fauci
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D002460:Cell Line; D002999:Clone Cells / Q000378:metabolism; D003470:Culture Media; D000939:Epitopes; D006801:Humans; D007370:Interferon Type I / Q000502:physiology*; D007371:Interferon-gamma / Q000502:physiology*; D007376:Interleukin-2 / Q000502:physiology; D008213:Lymphocyte Activation; D008222:Lymphokines / Q000096:biosynthesis* / Q000302:isolation & purification / Q000502:physiology; D008262:Macrophage Activation; D016215:Macrophage-Activating Factors; D008264:Macrophages / Q000276:immunology; D010587:Phagocytosis; D010835:Phytohemagglutinins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology / Q000378:metabolism*
D000945:Antigens, Differentiation, T-Lymphocyte; D000954:Antigens, Surface; D003470:Culture Media; D000939:Epitopes; D007370:Interferon Type I; D007376:Interleukin-2; D008222:Lymphokines; D016215:Macrophage-Activating Factors; D010835:Phytohemagglutinins; D007371:Interferon-gamma