Abstract
A protein factor which induces high levels of gamma interferon (IFN-gamma) in resting splenic nonadherent cells was isolated from the sera of mice with generalized inflammation caused by endotoxic shock. The factor was highly purified by ammonium sulfate precipitation followed by ion-exchange column chromatography on DEAE-Sepharose, molecular sieving on Ultrogel AcA 44, and hydrophobic column chromatography with phenyl-Sepharose. It was further purified to apparent homogeneity by polyacrylamide gel electrophoresis. It induced IFN-gamma production in a dose-dependent manner in the presence of interleukin-2, monoclonal anti-CD3 antibody (anti-CD3 MAb), or concanavalin A (ConA) in spleen cells deprived of plastic plate- and nylon wool-adherent cells. Anti-CD3 MAb induced the highest level of production of the three. The factor, interleukin-2, anti-CD3 MAb, or ConA alone induced a trace of or no detectable IFN-gamma in these cells. The factor also exhibited an accessory function during proliferation in these cells in the presence of a suboptimal dose of ConA. However, the factor failed to stimulate IFN-gamma production when staphylococcal enterotoxin A, a superantigenic T-cell mitogen, was employed. Treatment with pronase or heat abolished these activities. These studies confirm the existence of a soluble protein factor which is able to exhibit a novel accessory function in IFN-gamma production in resting T or natural killer cells. It will be of interest to compare this factor with the recently cloned human natural killer stimulatory factor (NKSF/IL-12).
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- Antonelli G., Dianzani F., Van Damme J., Amicucci P., De Marco F., Cefaro A. A macrophage-derived factor different from interleukin 1 and able to induce interferon-gamma and lymphoproliferation in resting T lymphocytes. Cell Immunol. 1988 May;113(2):376–386. doi: 10.1016/0008-8749(88)90035-4. [DOI] [PubMed] [Google Scholar]
- Arbeit R. D., Leary P. L., Levin M. J. Gamma interferon production by combinations of human peripheral blood lymphocytes, monocytes, and cultured macrophages. Infect Immun. 1982 Feb;35(2):383–390. doi: 10.1128/iai.35.2.383-390.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blanchard D. K., Djeu J. Y., Klein T. W., Friedman H., Stewart W. E., 2nd Interferon-gamma induction by lipopolysaccharide: dependence on interleukin 2 and macrophages. J Immunol. 1986 Feb 1;136(3):963–970. [PubMed] [Google Scholar]
- Chan S. H., Perussia B., Gupta J. W., Kobayashi M., Pospísil M., Young H. A., Wolf S. F., Young D., Clark S. C., Trinchieri G. Induction of interferon gamma production by natural killer cell stimulatory factor: characterization of the responder cells and synergy with other inducers. J Exp Med. 1991 Apr 1;173(4):869–879. doi: 10.1084/jem.173.4.869. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Croll A. D., Morris A. G. The regulation of gamma-interferon production by interleukins 1 and 2. Cell Immunol. 1986 Oct 1;102(1):33–42. doi: 10.1016/0008-8749(86)90323-0. [DOI] [PubMed] [Google Scholar]
- Croll A. D., Wilkinson M. F., Morris A. G. Gamma-interferon production by human low-density lymphocytes induced by T-cell mitogens. Immunology. 1986 Aug;58(4):641–646. [PMC free article] [PubMed] [Google Scholar]
- Grabstein K., Dower S., Gillis S., Urdal D., Larsen A. Expression of interleukin 2, interferon-gamma, and the IL 2 receptor by human peripheral blood lymphocytes. J Immunol. 1986 Jun 15;136(12):4503–4508. [PubMed] [Google Scholar]
- Gubler U., Chua A. O., Schoenhaut D. S., Dwyer C. M., McComas W., Motyka R., Nabavi N., Wolitzky A. G., Quinn P. M., Familletti P. C. Coexpression of two distinct genes is required to generate secreted bioactive cytotoxic lymphocyte maturation factor. Proc Natl Acad Sci U S A. 1991 May 15;88(10):4143–4147. doi: 10.1073/pnas.88.10.4143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Handa K., Suzuki R., Matsui H., Shimizu Y., Kumagai K. Natural killer (NK) cells as a responder to interleukin 2 (IL 2). II. IL 2-induced interferon gamma production. J Immunol. 1983 Feb;130(2):988–992. [PubMed] [Google Scholar]
- Heremans H., Van Damme J., Dillen C., Dijkmans R., Billiau A. Interferon gamma, a mediator of lethal lipopolysaccharide-induced Shwartzman-like shock reactions in mice. J Exp Med. 1990 Jun 1;171(6):1853–1869. doi: 10.1084/jem.171.6.1853. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Janeway C. A., Jr, Carding S., Jones B., Murray J., Portoles P., Rasmussen R., Rojo J., Saizawa K., West J., Bottomly K. CD4+ T cells: specificity and function. Immunol Rev. 1988 Jan;101:39–80. doi: 10.1111/j.1600-065x.1988.tb00732.x. [DOI] [PubMed] [Google Scholar]
- Kasahara T., Hooks J. J., Dougherty S. F., Oppenheim J. J. Interleukin 2-mediated immune interferon (IFN-gamma) production by human T cells and T cell subsets. J Immunol. 1983 Apr;130(4):1784–1789. [PubMed] [Google Scholar]
- Kawase I., Brooks C. G., Kuribayashi K., Olabuenaga S., Newman W., Gillis S., Henney C. S. Interleukin 2 induces gamma-interferon production: participation of macrophages and NK-like cells. J Immunol. 1983 Jul;131(1):288–292. [PubMed] [Google Scholar]
- Kelly C. D., Welte K., Murray H. W. Antigen-induced human interferon-gamma production. Differential dependence on interleukin 2 and its receptor. J Immunol. 1987 Oct 1;139(7):2325–2328. [PubMed] [Google Scholar]
- Kobayashi M., Fitz L., Ryan M., Hewick R. M., Clark S. C., Chan S., Loudon R., Sherman F., Perussia B., Trinchieri G. Identification and purification of natural killer cell stimulatory factor (NKSF), a cytokine with multiple biologic effects on human lymphocytes. J Exp Med. 1989 Sep 1;170(3):827–845. doi: 10.1084/jem.170.3.827. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Le J., Lin J. X., Henriksen-DeStefano D., Vilcek J. Bacterial lipopolysaccharide-induced interferon-gamma production: roles of interleukin 1 and interleukin 2. J Immunol. 1986 Jun 15;136(12):4525–4530. [PubMed] [Google Scholar]
- Lichtman A. H., Chin J., Schmidt J. A., Abbas A. K. Role of interleukin 1 in the activation of T lymphocytes. Proc Natl Acad Sci U S A. 1988 Dec;85(24):9699–9703. doi: 10.1073/pnas.85.24.9699. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matsumura H., Nakano M. Endotoxin-induced interferon-gamma production in culture cells derived from BCG-infected C3H/HeJ mice. J Immunol. 1988 Jan 15;140(2):494–500. [PubMed] [Google Scholar]
- Mosmann T. R., Cherwinski H., Bond M. W., Giedlin M. A., Coffman R. L. Two types of murine helper T cell clone. I. Definition according to profiles of lymphokine activities and secreted proteins. J Immunol. 1986 Apr 1;136(7):2348–2357. [PubMed] [Google Scholar]
- Mukaida N., Kasahara T., Hosoi J., Shioiri-Nakano K., Kawai T. Effects of anti-Tac antibody on the response of large granular lymphocytes to interleukin-2. Immunology. 1986 Jan;57(1):137–143. [PMC free article] [PubMed] [Google Scholar]
- Nakamura K., Okamura H., Wada M., Nagata K., Tamura T. Endotoxin-induced serum factor that stimulates gamma interferon production. Infect Immun. 1989 Feb;57(2):590–595. doi: 10.1128/iai.57.2.590-595.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Okamura H., Kawaguchi K., Shoji K., Kawade Y. High-level induction of gamma interferon with various mitogens in mice pretreated with Propionibacterium acnes. Infect Immun. 1982 Nov;38(2):440–443. doi: 10.1128/iai.38.2.440-443.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Okamura H., Wada M., Nagata K., Tamura T., Shoji K. Induction of murine gamma interferon production by lipopolysaccharide and interleukin-2 in Propionibacterium acnes-induced peritoneal exudate cells. Infect Immun. 1987 Feb;55(2):335–341. doi: 10.1128/iai.55.2.335-341.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ortaldo J. R., Mason A. T., Gerard J. P., Henderson L. E., Farrar W., Hopkins R. F., 3rd, Herberman R. B., Rabin H. Effects of natural and recombinant IL 2 on regulation of IFN gamma production and natural killer activity: lack of involvement of the Tac antigen for these immunoregulatory effects. J Immunol. 1984 Aug;133(2):779–783. [PubMed] [Google Scholar]
- Pearlstein K. T., Palladino M. A., Welte K., Vilcek J. Purified human interleukin-2 enhances induction of immune interferon. Cell Immunol. 1983 Aug;80(1):1–9. doi: 10.1016/0008-8749(83)90088-6. [DOI] [PubMed] [Google Scholar]
- Reem G. H., Yeh N. H. Interleukin 2 regulates expression of its receptor and synthesis of gamma interferon by human T lymphocytes. Science. 1984 Jul 27;225(4660):429–430. doi: 10.1126/science.6429853. [DOI] [PubMed] [Google Scholar]
- Snapper C. M., Paul W. E. Interferon-gamma and B cell stimulatory factor-1 reciprocally regulate Ig isotype production. Science. 1987 May 22;236(4804):944–947. doi: 10.1126/science.3107127. [DOI] [PubMed] [Google Scholar]
- Stern A. S., Podlaski F. J., Hulmes J. D., Pan Y. C., Quinn P. M., Wolitzky A. G., Familletti P. C., Stremlo D. L., Truitt T., Chizzonite R. Purification to homogeneity and partial characterization of cytotoxic lymphocyte maturation factor from human B-lymphoblastoid cells. Proc Natl Acad Sci U S A. 1990 Sep;87(17):6808–6812. doi: 10.1073/pnas.87.17.6808. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Trinchieri G., Matsumoto-Kobayashi M., Clark S. C., Seehra J., London L., Perussia B. Response of resting human peripheral blood natural killer cells to interleukin 2. J Exp Med. 1984 Oct 1;160(4):1147–1169. doi: 10.1084/jem.160.4.1147. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wada M., Okamura H., Nagata K., Shimoyama T., Kawade Y. Cellular mechanisms in in vivo production of gamma interferon induced by lipopolysaccharide in mice infected with Mycobacterium bovis BCG. J Interferon Res. 1985 Summer;5(3):431–443. doi: 10.1089/jir.1985.5.431. [DOI] [PubMed] [Google Scholar]
- Weaver C. T., Hawrylowicz C. M., Unanue E. R. T helper cell subsets require the expression of distinct costimulatory signals by antigen-presenting cells. Proc Natl Acad Sci U S A. 1988 Nov;85(21):8181–8185. doi: 10.1073/pnas.85.21.8181. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Wilson A. B., Harris J. M., Coombs R. R. Interleukin-2-induced production of interferon-gamma by resting human T cells and large granular lymphocytes: requirement for accessory cell factors, including interleukin-1. Cell Immunol. 1988 Apr 15;113(1):130–142. doi: 10.1016/0008-8749(88)90012-3. [DOI] [PubMed] [Google Scholar]
- Wolf S. F., Temple P. A., Kobayashi M., Young D., Dicig M., Lowe L., Dzialo R., Fitz L., Ferenz C., Hewick R. M. Cloning of cDNA for natural killer cell stimulatory factor, a heterodimeric cytokine with multiple biologic effects on T and natural killer cells. J Immunol. 1991 May 1;146(9):3074–3081. [PubMed] [Google Scholar]