Interleukin-2-induced production of interferon-gamma by resting human T cells and large granular lymphocytes: requirement for accessory cell factors, including interleukin-1.
Between 5 and 20% of normal human lymphocytes were found to synthesize interferon-gamma (IFN-gamma) in primary cultures with recombinant interleukin-2 (rIL-2). After 22 hr, IFN-gamma-producing cells included CD5+ T lymphocytes, CD16+ large granular lymphocytes (LGL), and a population of CD5-, CD16- blast cells. Only a small proportion (0-7%) of IFN-gamma-synthesizing cells expressed HLA-DR. The production of IFN-gamma by all rIL-2-responding lymphocyte subsets was shown to require the presence of DR+ accessory cells, probably including nonadherent, esterase-negative monocytes and/or dendritic cells. Accessory cell function in lymphocyte preparations depleted of DR+ cells, or in purified (greater than or equal to 95%) suspensions of LGL, was fully replaced either by addition of 2% autologous, adherent monocytes or by monocyte culture supernatant. The activity of monocyte supernatant was greatly reduced by treatment with antiserum specific for human interleukin-1 beta (IL-1 beta), although a combination of rIL-1 beta and rIL-2 failed to stimulate IFN-gamma production in DR- lymphocytes. These results indicate that rIL-2-induced IFN-gamma synthesis in both T cells and LGL requires the synergistic activity of IL-1, and possibly of one or more other monokines, as yet unidentified.
D000938:Antigen-Presenting Cells / Q000276:immunology*; D002448:Cell Adhesion; D002450:Cell Communication; D002469:Cell Separation; D002474:Cell-Free System; D046508:Culture Techniques; D006684:HLA-DR Antigens; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis*; D007375:Interleukin-1 / Q000276:immunology / Q000502:physiology*; D007376:Interleukin-2 / Q000494:pharmacology*; D007399:Interphase; D007694:Killer Cells, Natural / Q000145:classification / Q000166:cytology / Q000378:metabolism*; D007700:Kinetics; D009000:Monocytes / Q000276:immunology; D010641:Phenotype; D011994:Recombinant Proteins / Q000494:pharmacology; D013601:T-Lymphocytes / Q000145:classification / Q000166:cytology / Q000378:metabolism*
D006684:HLA-DR Antigens; D007375:Interleukin-1; D007376:Interleukin-2; D011994:Recombinant Proteins; D007371:Interferon-gamma