Abstract
In order to examine the possibility that a local chronic infection can induce organ-specific autoimmune disease, we inoculated unilateral kidneys with viable Listeria monocytogenes (intrarenal infection). The delayed footpad reaction against syngeneic kidney homogenate (KH) became positive from 1 week after initiating the intrarenal infection. A proliferative response of the spleen T cells from the infected mice was also observed against KH from 1 week after initiating the intrarenal infection, but no such response was seen against liver homogenate (LH). In contrast, an intravenous Listeria infection did not induce a delayed footpad reaction or proliferative response against KH, suggesting that these autoimmune responses were not caused by molecular mimicry between renal antigens and Listeria antigens. Furthermore, the ability to transfer the autoimmune response of spleen T cells from intrarenally infected mice was examined. The transferred mice showed a positive delayed footpad reaction against KH and an interstitial infiltration of mononuclear cells in their kidneys. These results demonstrate that the intrarenal Listeria infection induced renal autoantigen-specific T cells, which subsequently induced an autoimmune interstitial nephritis (AIN). The autoreactive T cells were all induced without immunization by autoantigens mixed with complete Freund's adjuvant. Based on these findings, we propose that a local bacterial infection may induce an autoimmune response against autoantigens in the infected organ and subsequently trigger organ-specific autoimmune disease.
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- Bessen D., Jones K. F., Fischetti V. A. Evidence for two distinct classes of streptococcal M protein and their relationship to rheumatic fever. J Exp Med. 1989 Jan 1;169(1):269–283. doi: 10.1084/jem.169.1.269. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Billiau A., Heremans H., Vandekerckhove F., Dijkmans R., Sobis H., Meulepas E., Carton H. Enhancement of experimental allergic encephalomyelitis in mice by antibodies against IFN-gamma. J Immunol. 1988 Mar 1;140(5):1506–1510. [PubMed] [Google Scholar]
- Elson C. J., Barker R. N., Thompson S. J., Williams N. A. Immunologically ignorant autoreactive T cells, epitope spreading and repertoire limitation. Immunol Today. 1995 Feb;16(2):71–76. doi: 10.1016/0167-5699(95)80091-3. [DOI] [PubMed] [Google Scholar]
- Goverman J., Woods A., Larson L., Weiner L. P., Hood L., Zaller D. M. Transgenic mice that express a myelin basic protein-specific T cell receptor develop spontaneous autoimmunity. Cell. 1993 Feb 26;72(4):551–560. doi: 10.1016/0092-8674(93)90074-z. [DOI] [PubMed] [Google Scholar]
- Hagerty D. T., Allen P. M. Processing and presentation of self and foreign antigens by the renal proximal tubule. J Immunol. 1992 Apr 15;148(8):2324–2330. [PubMed] [Google Scholar]
- Hart D. N., Fabre J. W. Endogenously produced Ia antigens within cells of convoluted tubules of rat kidney. J Immunol. 1981 Jun;126(6):2109–2113. [PubMed] [Google Scholar]
- Hiromatsu K., Yoshikai Y., Matsuzaki G., Ohga S., Muramori K., Matsumoto K., Bluestone J. A., Nomoto K. A protective role of gamma/delta T cells in primary infection with Listeria monocytogenes in mice. J Exp Med. 1992 Jan 1;175(1):49–56. doi: 10.1084/jem.175.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hsieh C. S., Macatonia S. E., Tripp C. S., Wolf S. F., O'Garra A., Murphy K. M. Development of TH1 CD4+ T cells through IL-12 produced by Listeria-induced macrophages. Science. 1993 Apr 23;260(5107):547–549. doi: 10.1126/science.8097338. [DOI] [PubMed] [Google Scholar]
- Kaufmann S. H. Immunity against intracellular bacteria: biological effector functions and antigen specificity of T lymphocytes. Curr Top Microbiol Immunol. 1988;138:141–176. [PubMed] [Google Scholar]
- Kingsley G., Sieper J. Current perspectives in reactive arthritis. Immunol Today. 1993 Aug;14(8):387–391. doi: 10.1016/0167-5699(93)90139-C. [DOI] [PubMed] [Google Scholar]
- Kirby J. A., Ikuta S., Clark K., Proud G., Lennard T. W., Taylor R. M. Renal allograft rejection: investigation of alloantigen presentation by cultured human renal epithelial cells. Immunology. 1991 Mar;72(3):411–417. [PMC free article] [PubMed] [Google Scholar]
- Neilson E. G., McCafferty E., Feldman A., Clayman M. D., Zakheim B., Korngold R. Spontaneous interstitial nephritis in kdkd mice. I. An experimental model of autoimmune renal disease. J Immunol. 1984 Nov;133(5):2560–2565. [PubMed] [Google Scholar]
- Neilson E. G., Phillips S. M. Murine interstitial nephritis. I. Analysis of disease susceptibility and its relationship of pleiomorphic gene products defining both immune-response genes and a restrictive requirement for cytotoxic T cells at H-2K. J Exp Med. 1982 Apr 1;155(4):1075–1085. doi: 10.1084/jem.155.4.1075. [DOI] [PMC free article] [PubMed] [Google Scholar]
- O'Brien R. L., Happ M. P., Dallas A., Palmer E., Kubo R., Born W. K. Stimulation of a major subset of lymphocytes expressing T cell receptor gamma delta by an antigen derived from Mycobacterium tuberculosis. Cell. 1989 May 19;57(4):667–674. doi: 10.1016/0092-8674(89)90135-9. [DOI] [PubMed] [Google Scholar]
- Ohga S., Yoshikai Y., Takeda Y., Hiromatsu K., Nomoto K. Sequential appearance of gamma/delta- and alpha/beta-bearing T cells in the peritoneal cavity during an i.p. infection with Listeria monocytogenes. Eur J Immunol. 1990 Mar;20(3):533–538. doi: 10.1002/eji.1830200311. [DOI] [PubMed] [Google Scholar]
- Powrie F., Coffman R. L. Cytokine regulation of T-cell function: potential for therapeutic intervention. Immunol Today. 1993 Jun;14(6):270–274. doi: 10.1016/0167-5699(93)90044-L. [DOI] [PubMed] [Google Scholar]
- Rose N. R., Neumann D. A., Herskowitz A. Autoimmune myocarditis: concepts and questions. Immunol Today. 1991 Aug;12(8):253–255. doi: 10.1016/0167-5699(91)90118-D. [DOI] [PubMed] [Google Scholar]
- Ruddle N. H., Bergman C. M., McGrath K. M., Lingenheld E. G., Grunnet M. L., Padula S. J., Clark R. B. An antibody to lymphotoxin and tumor necrosis factor prevents transfer of experimental allergic encephalomyelitis. J Exp Med. 1990 Oct 1;172(4):1193–1200. doi: 10.1084/jem.172.4.1193. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rugo H. S., O'Hanley P., Bishop A. G., Pearce M. K., Abrams J. S., Howard M., O'Garra A. Local cytokine production in a murine model of Escherichia coli pyelonephritis. J Clin Invest. 1992 Mar;89(3):1032–1039. doi: 10.1172/JCI115644. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sanui H., Yoshida S., Himeno K., Nomoto K. Delayed hypersensitivity to syngeneic testicular cells induced by intratesticular bacterial infection in guinea-pigs. Immunology. 1982 Jul;46(3):635–642. [PMC free article] [PubMed] [Google Scholar]
- Sher A., Coffman R. L. Regulation of immunity to parasites by T cells and T cell-derived cytokines. Annu Rev Immunol. 1992;10:385–409. doi: 10.1146/annurev.iy.10.040192.002125. [DOI] [PubMed] [Google Scholar]
- Sinha A. A., Lopez M. T., McDevitt H. O. Autoimmune diseases: the failure of self tolerance. Science. 1990 Jun 15;248(4961):1380–1388. doi: 10.1126/science.1972595. [DOI] [PubMed] [Google Scholar]
- Steblay R. W., Rudofsky U. Renal tubular disease and autoantibodies against tubular basement membrane induced in guinea pigs. J Immunol. 1971 Aug;107(2):589–594. [PubMed] [Google Scholar]
- Ueda S., Wakashin M., Wakashin Y., Yoshida H., Azemoto R., Iesato K., Mori T., Mori Y., Ogawa M., Okuda K. Autoimmune interstitial nephritis induced in inbred mice. Analysis of mouse tubular basement membrane antigen and genetic control of immune response to it. Am J Pathol. 1988 Aug;132(2):304–318. [PMC free article] [PubMed] [Google Scholar]
- Utz U., Biddison W. E., McFarland H. F., McFarlin D. E., Flerlage M., Martin R. Skewed T-cell receptor repertoire in genetically identical twins correlates with multiple sclerosis. Nature. 1993 Jul 15;364(6434):243–247. doi: 10.1038/364243a0. [DOI] [PubMed] [Google Scholar]
- Weiss R. A., Madaio M. P., Tomaszewski J. E., Kelly C. J. T cells reactive to an inducible heat shock protein induce disease in toxin-induced interstitial nephritis. J Exp Med. 1994 Dec 1;180(6):2239–2250. doi: 10.1084/jem.180.6.2239. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Williams R. O., Feldmann M., Maini R. N. Anti-tumor necrosis factor ameliorates joint disease in murine collagen-induced arthritis. Proc Natl Acad Sci U S A. 1992 Oct 15;89(20):9784–9788. doi: 10.1073/pnas.89.20.9784. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Young R. A., Elliott T. J. Stress proteins, infection, and immune surveillance. Cell. 1989 Oct 6;59(1):5–8. doi: 10.1016/0092-8674(89)90861-1. [DOI] [PubMed] [Google Scholar]
- Zakheim B., McCafferty E., Phillips S. M., Clayman M., Neilson E. G. Murine interstitial nephritis. II. The adoptive transfer of disease with immune T lymphocytes produces a phenotypically complex interstitial lesion. J Immunol. 1984 Jul;133(1):234–239. [PubMed] [Google Scholar]