Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1988 Apr;72(1):91–97.

Features of renal vasculitis in autoimmune MRL lpr/lpr mice: phenotypes and functional properties of infiltrating cells.

A Tarkowski 1, R Jonsson 1, R Sanchez 1, L Klareskog 1, W J Koopman 1
PMCID: PMC1541495  PMID: 3293853

Abstract

MRL lpr/lpr (MRL/1) mice spontaneously develop a widespread renal vasculitis. The majority of the cells in vasculitic lesions are bright Ly-1, L3T4 and la-positive in contrast to the cells found in lymph nodes and spleens of the old MRL/1 mice. However, despite differences in phenotypical patterns, B and T cells from arteritic lesions do not differ from mononuclear cells (MNC) eluted from MRL/1 lymph nodes with regard to the frequency of IgG secreting cells and the proliferative responses to Concanavalin A (Con A). Co-culture experiments with congeneic MRL+/+ (MRL/n) spleen cells indicate that the poor response to Con A of the MNC eluted from vasculitic lesions is, unlike the case of lymph node MNC, due to suppressive action of vasculitic cells on the indicator cell population. Further support for the activation status of infiltrating MHC in kidney vasculitic lesions, expressed by high in vivo uptake of 3H-thymidine, was obtained by autoradiography performed on frozen sections. The observed differences in phenotypic patterns and functional features between lymph node MNC and infiltrating vasculitic MNC indicate that different immune mechanisms may be responsible for the development of lymphadenopathy and vasculopathy, respectively in MRL/1 mouse.

Full text

PDF
91

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander E. L., Moyer C., Travlos G. S., Roths J. B., Murphy E. D. Two histopathologic types of inflammatory vascular disease in MRL/Mp autoimmune mice. Model for human vasculitis in connective tissue disease. Arthritis Rheum. 1985 Oct;28(10):1146–1155. doi: 10.1002/art.1780281011. [DOI] [PubMed] [Google Scholar]
  2. Andrews B. S., Eisenberg R. A., Theofilopoulos A. N., Izui S., Wilson C. B., McConahey P. J., Murphy E. D., Roths J. B., Dixon F. J. Spontaneous murine lupus-like syndromes. Clinical and immunopathological manifestations in several strains. J Exp Med. 1978 Nov 1;148(5):1198–1215. doi: 10.1084/jem.148.5.1198. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Berden J. H., Hang L., McConahey P. J., Dixon F. J. Analysis of vascular lesions in murine SLE. I. Association with serologic abnormalities. J Immunol. 1983 Apr;130(4):1699–1705. [PubMed] [Google Scholar]
  4. Bergroth V., Konttinen Y. T., Nykänen P., von Essen R., Koota K. Proliferating cells in the synovial fluid in rheumatic disease. An analysis with autoradiography-immunoperoxidase double staining. Scand J Immunol. 1985 Oct;22(4):383–388. doi: 10.1111/j.1365-3083.1985.tb01896.x. [DOI] [PubMed] [Google Scholar]
  5. Claesson K., Forsum U., Klareskog L., Andréen T., Larsson E., Frödin L., Tufveson G. Tissue distribution of T-lymphocytes and Ia-expressing cells in rat kidney grafts. Scand J Immunol. 1985 Sep;22(3):273–278. doi: 10.1111/j.1365-3083.1985.tb01881.x. [DOI] [PubMed] [Google Scholar]
  6. Cochrane C. G., Koffler D. Immune complex disease in experimental animals and man. Adv Immunol. 1973;16(0):185–264. doi: 10.1016/s0065-2776(08)60298-9. [DOI] [PubMed] [Google Scholar]
  7. Czerkinsky C. C., Tarkowski A., Nilsson L. A., Ouchterlony O., Nygren H., Gretzer C. Reverse enzyme-linked immunospot assay (RELISPOT) for the detection of cells secreting immunoreactive substances. J Immunol Methods. 1984 Sep 4;72(2):489–496. doi: 10.1016/0022-1759(84)90017-6. [DOI] [PubMed] [Google Scholar]
  8. DIXON F. J., VAZQUEZ J. J., WEIGLE W. O., COCHRANE C. G. Pathogenesis of serum sickness. AMA Arch Pathol. 1958 Jan;65(1):18–28. [PubMed] [Google Scholar]
  9. Dohlsten M., Lindén O., Hedlund G., Sjögren H. O., Diamantstein T., Carlsson R. Synergistic action of gamma interferon and catalase to reverse the suppressive effect of peritoneal macrophages on concanavalin A-induced lymphocyte proliferation. Scand J Immunol. 1986 Jul;24(1):49–58. doi: 10.1111/j.1365-3083.1986.tb02069.x. [DOI] [PubMed] [Google Scholar]
  10. Fauci A. S., Haynes B., Katz P. The spectrum of vasculitis: clinical, pathologic, immunologic and therapeutic considerations. Ann Intern Med. 1978 Nov;89(5 Pt 1):660–676. doi: 10.7326/0003-4819-89-5-660. [DOI] [PubMed] [Google Scholar]
  11. Hall B. M., Bishop G. A., Duggin G. G., Horvath J. S., Philips J., Tiller D. J. Increased expression of HLA-DR antigens on renal tubular cells in renal transplants: relevance to the rejection response. Lancet. 1984 Aug 4;2(8397):247–251. doi: 10.1016/s0140-6736(84)90297-6. [DOI] [PubMed] [Google Scholar]
  12. Hjelm E. M. Local cellular immune response in ascending urinary tract infection: occurrence of T-cells, immunoglobulin-producing cells, and Ia-expressing cells in rat urinary tract tissue. Infect Immun. 1984 Jun;44(3):627–632. doi: 10.1128/iai.44.3.627-632.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  14. Kincade P. W., Lee G., Watanabe T., Sun L., Scheid M. P. Antigens displayed on murine B lymphocyte precursors. J Immunol. 1981 Dec;127(6):2262–2268. [PubMed] [Google Scholar]
  15. Klareskog L., Forsum U., Scheynius A., Kabelitz D., Wigzell H. Evidence in support of a self-perpetuating HLA-DR-dependent delayed-type cell reaction in rheumatoid arthritis. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3632–3636. doi: 10.1073/pnas.79.11.3632. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Klareskog L., Forsum U., Wigzell H. Murine synovial intima contains I-A-, I-E/C-positive bone-marrow-derived cells. Scand J Immunol. 1981 May;15(5):509–514. doi: 10.1111/j.1365-3083.1982.tb00677.x. [DOI] [PubMed] [Google Scholar]
  17. Klareskog L., Holmdahl R., Rubin K., Victorin A., Lindgren J. A. Different populations of rheumatoid adherent cells mediate activation versus suppression of T lymphocyte proliferation. Arthritis Rheum. 1985 Aug;28(8):863–872. doi: 10.1002/art.1780280805. [DOI] [PubMed] [Google Scholar]
  18. Ledbetter J. A., Herzenberg L. A. Xenogeneic monoclonal antibodies to mouse lymphoid differentiation antigens. Immunol Rev. 1979;47:63–90. doi: 10.1111/j.1600-065x.1979.tb00289.x. [DOI] [PubMed] [Google Scholar]
  19. Lycke N. A sensitive method for the detection of specific antibody production in different isotypes from single lamina propria plasma cells. Scand J Immunol. 1986 Oct;24(4):393–403. doi: 10.1111/j.1365-3083.1986.tb02127.x. [DOI] [PubMed] [Google Scholar]
  20. Malek T. R., Robb R. J., Shevach E. M. Identification and initial characterization of a rat monoclonal antibody reactive with the murine interleukin 2 receptor-ligand complex. Proc Natl Acad Sci U S A. 1983 Sep;80(18):5694–5698. doi: 10.1073/pnas.80.18.5694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Metzger Z., Hoffeld J. T., Oppenheim J. J. Macrophage-mediated suppression. I. Evidence for participation of both hdyrogen peroxide and prostaglandins in suppression of murine lymphocyte proliferation. J Immunol. 1980 Feb;124(2):983–988. [PubMed] [Google Scholar]
  22. Morse H. C., 3rd, Davidson W. F., Yetter R. A., Murphy E. D., Roths J. B., Coffman R. L. Abnormalities induced by the mutant gene Ipr: expansion of a unique lymphocyte subset. J Immunol. 1982 Dec;129(6):2612–2615. [PubMed] [Google Scholar]
  23. Moyer C. F., Strandberg J. D., Reinisch C. L. Systemic mononuclear-cell vasculitis in MRL/Mp-lpr/lpr mice. A histologic and immunocytochemical analysis. Am J Pathol. 1987 May;127(2):229–242. [PMC free article] [PubMed] [Google Scholar]
  24. Pierres A., Naquet P., Van Agthoven A., Bekkhoucha F., Denizot F., Mishal Z., Schmitt-Verhulst A. M., Pierres M. A rat anti-mouse T4 monoclonal antibody (H129.19) inhibits the proliferation of Ia-reactive T cell clones and delineates two phenotypically distinct (T4+, Lyt-2,3-, and T4-, Lyt-2,3+) subsets among anti-Ia cytolytic T cell clones. J Immunol. 1984 Jun;132(6):2775–2782. [PubMed] [Google Scholar]
  25. Springer T., Galfré G., Secher D. S., Milstein C. Mac-1: a macrophage differentiation antigen identified by monoclonal antibody. Eur J Immunol. 1979 Apr;9(4):301–306. doi: 10.1002/eji.1830090410. [DOI] [PubMed] [Google Scholar]
  26. Tarkowski A., Czerkinsky C., Nilsson L. A. Detection of IgG rheumatoid factor secreting cells in autoimmune MRL/1 mice: a kinetic study. Clin Exp Immunol. 1984 Oct;58(1):7–12. [PMC free article] [PubMed] [Google Scholar]
  27. Tarkowski A., Jonsson R., Holmdahl R., Klareskog L. Immunohistochemical characterization of synovial cells in arthritic MRL-lpr/lpr mice. Arthritis Rheum. 1987 Jan;30(1):75–82. doi: 10.1002/art.1780300110. [DOI] [PubMed] [Google Scholar]
  28. Wofsy D., Hardy R. R., Seaman W. E. The proliferating cells in autoimmune MRL/lpr mice lack L3T4, an antigen on "helper" T cells that is involved in the response to class II major histocompatibility antigens. J Immunol. 1984 Jun;132(6):2686–2689. [PubMed] [Google Scholar]
  29. Zembala M., Lemmel E. M. Inhibitory factor(s) of lymphoproliferation produced by synovial fluid mononuclear cells from rheumatoid arthritis patients: the role of monocytes in suppression. J Immunol. 1980 Sep;125(3):1087–1092. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES