Abstract
Recently, it has been shown that interleukin-7 (IL-7) is able to induce secretion of cytokines and tumoricidal activity by human monocytes. This study shows that treatment of murine macrophages infected with Leishmania major with IL-7 without any other stimulus reduced the percentage of infected cells, as well as the parasite burden per cell, in a dose-dependent manner to a limited degree (45% reduction of the number of amastigotes per 100 macrophages). Simultaneous treatment of macrophages with gamma interferon and IL-7 led to nearly complete (> 99%) elimination of amastigotes. Addition of anti-tumor necrosis factor alpha or N omega-monomethyl-L-arginine acetate reversed the leishmanicidal effects of IL-7, and production of nitric oxide was induced in the presence of IL-7.
Full text
PDF




Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alderson M. R., Sassenfeld H. M., Widmer M. B. Interleukin 7 enhances cytolytic T lymphocyte generation and induces lymphokine-activated killer cells from human peripheral blood. J Exp Med. 1990 Aug 1;172(2):577–587. doi: 10.1084/jem.172.2.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alderson M. R., Tough T. W., Ziegler S. F., Grabstein K. H. Interleukin 7 induces cytokine secretion and tumoricidal activity by human peripheral blood monocytes. J Exp Med. 1991 Apr 1;173(4):923–930. doi: 10.1084/jem.173.4.923. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bazin H., Xhurdebise L. M., Burtonboy G., Lebacq A. M., De Clercq L., Cormont F. Rat monoclonal antibodies. I. Rapid purification from in vitro culture supernatants. J Immunol Methods. 1984 Feb 10;66(2):261–269. doi: 10.1016/0022-1759(84)90337-5. [DOI] [PubMed] [Google Scholar]
- Bertagnolli M., Herrmann S. IL-7 supports the generation of cytotoxic T lymphocytes from thymocytes. Multiple lymphokines required for proliferation and cytotoxicity. J Immunol. 1990 Sep 15;145(6):1706–1712. [PubMed] [Google Scholar]
- Bogdan C., Moll H., Solbach W., Röllinghoff M. Tumor necrosis factor-alpha in combination with interferon-gamma, but not with interleukin 4 activates murine macrophages for elimination of Leishmania major amastigotes. Eur J Immunol. 1990 May;20(5):1131–1135. doi: 10.1002/eji.1830200528. [DOI] [PubMed] [Google Scholar]
- Bogdan C., Stenger S., Röllinghoff M., Solbach W. Cytokine interactions in experimental cutaneous leishmaniasis. Interleukin 4 synergizes with interferon-gamma to activate murine macrophages for killing of Leishmania major amastigotes. Eur J Immunol. 1991 Feb;21(2):327–333. doi: 10.1002/eji.1830210213. [DOI] [PubMed] [Google Scholar]
- Chazen G. D., Pereira G. M., LeGros G., Gillis S., Shevach E. M. Interleukin 7 is a T-cell growth factor. Proc Natl Acad Sci U S A. 1989 Aug;86(15):5923–5927. doi: 10.1073/pnas.86.15.5923. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Conlon P. J., Morrissey P. J., Nordan R. P., Grabstein K. H., Prickett K. S., Reed S. G., Goodwin R., Cosman D., Namen A. E. Murine thymocytes proliferate in direct response to interleukin-7. Blood. 1989 Sep;74(4):1368–1373. [PubMed] [Google Scholar]
- Ding A. H., Nathan C. F., Stuehr D. J. Release of reactive nitrogen intermediates and reactive oxygen intermediates from mouse peritoneal macrophages. Comparison of activating cytokines and evidence for independent production. J Immunol. 1988 Oct 1;141(7):2407–2412. [PubMed] [Google Scholar]
- Goodwin R. G., Lupton S., Schmierer A., Hjerrild K. J., Jerzy R., Clevenger W., Gillis S., Cosman D., Namen A. E. Human interleukin 7: molecular cloning and growth factor activity on human and murine B-lineage cells. Proc Natl Acad Sci U S A. 1989 Jan;86(1):302–306. doi: 10.1073/pnas.86.1.302. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Grabstein K. H., Namen A. E., Shanebeck K., Voice R. F., Reed S. G., Widmer M. B. Regulation of T cell proliferation by IL-7. J Immunol. 1990 Apr 15;144(8):3015–3020. [PubMed] [Google Scholar]
- Green S. J., Crawford R. M., Hockmeyer J. T., Meltzer M. S., Nacy C. A. Leishmania major amastigotes initiate the L-arginine-dependent killing mechanism in IFN-gamma-stimulated macrophages by induction of tumor necrosis factor-alpha. J Immunol. 1990 Dec 15;145(12):4290–4297. [PubMed] [Google Scholar]
- Hickman C. J., Crim J. A., Mostowski H. S., Siegel J. P. Regulation of human cytotoxic T lymphocyte development by IL-7. J Immunol. 1990 Oct 15;145(8):2415–2420. [PubMed] [Google Scholar]
- Ho J. L., Reed S. G., Sobel J., Arruda S., He S. H., Wick E. A., Grabstein K. H. Interleukin-3 induces antimicrobial activity against Leishmania amazonensis and Trypanosoma cruzi and tumoricidal activity in human peripheral blood-derived macrophages. Infect Immun. 1992 May;60(5):1984–1993. doi: 10.1128/iai.60.5.1984-1993.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Howard J. G. Immunological regulation and control of experimental leishmaniasis. Int Rev Exp Pathol. 1986;28:79–116. [PubMed] [Google Scholar]
- Jicha D. L., Mulé J. J., Rosenberg S. A. Interleukin 7 generates antitumor cytotoxic T lymphocytes against murine sarcomas with efficacy in cellular adoptive immunotherapy. J Exp Med. 1991 Dec 1;174(6):1511–1515. doi: 10.1084/jem.174.6.1511. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kos F. J., Müllbacher A. Induction of primary anti-viral cytotoxic T cells by in vitro stimulation with short synthetic peptide and interleukin-7. Eur J Immunol. 1992 Dec;22(12):3183–3185. doi: 10.1002/eji.1830221224. [DOI] [PubMed] [Google Scholar]
- Langermans J. A., Van der Hulst M. E., Nibbering P. H., Hiemstra P. S., Fransen L., Van Furth R. IFN-gamma-induced L-arginine-dependent toxoplasmastatic activity in murine peritoneal macrophages is mediated by endogenous tumor necrosis factor-alpha. J Immunol. 1992 Jan 15;148(2):568–574. [PubMed] [Google Scholar]
- Liew F. Y. Functional heterogeneity of CD4+ T cells in leishmaniasis. Immunol Today. 1989 Feb;10(2):40–45. doi: 10.1016/0167-5699(89)90302-2. [DOI] [PubMed] [Google Scholar]
- Liew F. Y., Li Y., Millott S. Tumor necrosis factor-alpha synergizes with IFN-gamma in mediating killing of Leishmania major through the induction of nitric oxide. J Immunol. 1990 Dec 15;145(12):4306–4310. [PubMed] [Google Scholar]
- Liew F. Y., Li Y., Moss D., Parkinson C., Rogers M. V., Moncada S. Resistance to Leishmania major infection correlates with the induction of nitric oxide synthase in murine macrophages. Eur J Immunol. 1991 Dec;21(12):3009–3014. doi: 10.1002/eji.1830211216. [DOI] [PubMed] [Google Scholar]
- Morrissey P. J., Goodwin R. G., Nordan R. P., Anderson D., Grabstein K. H., Cosman D., Sims J., Lupton S., Acres B., Reed S. G. Recombinant interleukin 7, pre-B cell growth factor, has costimulatory activity on purified mature T cells. J Exp Med. 1989 Mar 1;169(3):707–716. doi: 10.1084/jem.169.3.707. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Murray H. W., Rubin B. Y., Rothermel C. D. Killing of intracellular Leishmania donovani by lymphokine-stimulated human mononuclear phagocytes. Evidence that interferon-gamma is the activating lymphokine. J Clin Invest. 1983 Oct;72(4):1506–1510. doi: 10.1172/JCI111107. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Namen A. E., Lupton S., Hjerrild K., Wignall J., Mochizuki D. Y., Schmierer A., Mosley B., March C. J., Urdal D., Gillis S. Stimulation of B-cell progenitors by cloned murine interleukin-7. Nature. 1988 Jun 9;333(6173):571–573. doi: 10.1038/333571a0. [DOI] [PubMed] [Google Scholar]
- Naume B., Espevik T. Effects of IL-7 and IL-2 on highly enriched CD56+ natural killer cells. A comparative study. J Immunol. 1991 Oct 1;147(7):2208–2214. [PubMed] [Google Scholar]
- Okazaki H., Ito M., Sudo T., Hattori M., Kano S., Katsura Y., Minato N. IL-7 promotes thymocyte proliferation and maintains immunocompetent thymocytes bearing alpha beta or gamma delta T-cell receptors in vitro: synergism with IL-2. J Immunol. 1989 Nov 1;143(9):2917–2922. [PubMed] [Google Scholar]
- Scott P., Pearce E., Cheever A. W., Coffman R. L., Sher A. Role of cytokines and CD4+ T-cell subsets in the regulation of parasite immunity and disease. Immunol Rev. 1989 Dec;112:161–182. doi: 10.1111/j.1600-065x.1989.tb00557.x. [DOI] [PubMed] [Google Scholar]
- Solbach W., Forberg K., Röllinghoff M. Effect of T-lymphocyte suppression on the parasite burden in Leishmania major-infected, genetically susceptible BALB/c mice. Infect Immun. 1986 Dec;54(3):909–912. doi: 10.1128/iai.54.3.909-912.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Spitalny G. L., Havell E. A. Monoclonal antibody to murine gamma interferon inhibits lymphokine-induced antiviral and macrophage tumoricidal activities. J Exp Med. 1984 May 1;159(5):1560–1565. doi: 10.1084/jem.159.5.1560. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stenger S., Solbach W., Röllinghoff M., Bogdan C. Cytokine interactions in experimental cutaneous leishmaniasis. II. Endogenous tumor necrosis factor-alpha production by macrophages is induced by the synergistic action of interferon (IFN)-gamma and interleukin (IL) 4 and accounts for the antiparasitic effect mediated by IFN-gamma and IL 4. Eur J Immunol. 1991 Jul;21(7):1669–1675. doi: 10.1002/eji.1830210713. [DOI] [PubMed] [Google Scholar]
- Theodos C. M., Povinelli L., Molina R., Sherry B., Titus R. G. Role of tumor necrosis factor in macrophage leishmanicidal activity in vitro and resistance to cutaneous leishmaniasis in vivo. Infect Immun. 1991 Aug;59(8):2839–2842. doi: 10.1128/iai.59.8.2839-2842.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Titus R. G., Sherry B., Cerami A. Tumor necrosis factor plays a protective role in experimental murine cutaneous leishmaniasis. J Exp Med. 1989 Dec 1;170(6):2097–2104. doi: 10.1084/jem.170.6.2097. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tushinski R. J., Oliver I. T., Guilbert L. J., Tynan P. W., Warner J. R., Stanley E. R. Survival of mononuclear phagocytes depends on a lineage-specific growth factor that the differentiated cells selectively destroy. Cell. 1982 Jan;28(1):71–81. doi: 10.1016/0092-8674(82)90376-2. [DOI] [PubMed] [Google Scholar]
- Vairo G., Hamilton J. A. CSF-1 stimulates Na+K+-ATPase mediated 86Rb+ uptake in mouse bone marrow-derived macrophages. Biochem Biophys Res Commun. 1985 Oct 15;132(1):430–437. doi: 10.1016/0006-291x(85)91040-x. [DOI] [PubMed] [Google Scholar]
- Watson J. D., Morrissey P. J., Namen A. E., Conlon P. J., Widmer M. B. Effect of IL-7 on the growth of fetal thymocytes in culture. J Immunol. 1989 Aug 15;143(4):1215–1222. [PubMed] [Google Scholar]
- Weiser W. Y., Pozzi L. M., David J. R. Human recombinant migration inhibitory factor activates human macrophages to kill Leishmania donovani. J Immunol. 1991 Sep 15;147(6):2006–2011. [PubMed] [Google Scholar]
- Ziegler S. F., Tough T. W., Franklin T. L., Armitage R. J., Alderson M. R. Induction of macrophage inflammatory protein-1 beta gene expression in human monocytes by lipopolysaccharide and IL-7. J Immunol. 1991 Oct 1;147(7):2234–2239. [PubMed] [Google Scholar]
