Skip to main content
NCBI home page
Immunology logoLink to Immunology
. 1987 Apr;60(4):611–616.

Sialadenitis in the MRL-l mouse: morphological and immunohistochemical characterization of resident and infiltrating cells.

R Jonsson, A Tarkowski, K Bäckman, R Holmdahl, L Klareskog
PMCID: PMC1453282  PMID: 3294576

Abstract

The MRL-lpr/lpr (MRL/l) mouse spontaneously develops an autoimmune disease associated with various rheumatic manifestations. We have studied the histological features of sialadenitis and utilized an immunohistochemical staining technique on frozen tissue sections to analyse the cellular composition of the salivary glands at varying stages of disease. Semiquantitative assessment of the infiltration disclosed a focal inflammation which started at 2 months of age and was progressive until 5 months of age in submandibular glands. A high frequency of Ly-1 and L3T4-positive cells was observed at all stages of sialadenitis, whereas Lyt-2 positive cells were found at a lower frequency. Ia expression was seen on a large proportion of the infiltrating cells and also on ductal and glandular epithelial cells in the vicinity of the inflammatory lesions. The presence of Ia antigens on many inflammatory as well as resident cells and the high frequency of lymphocytes with 'helper' phenotype may indicate a perpetuated immunological activation within salivary glands.

Full text

PDF
611

Images in this article

614Figure 3
on p.614

Selected References

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

  1. 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]
  2. Daniels T. E. Labial salivary gland biopsy in Sjögren's syndrome. Assessment as a diagnostic criterion in 362 suspected cases. Arthritis Rheum. 1984 Feb;27(2):147–156. doi: 10.1002/art.1780270205. [DOI] [PubMed] [Google Scholar]
  3. Fox R. I., Carstens S. A., Fong S., Robinson C. A., Howell F., Vaughan J. H. Use of monoclonal antibodies to analyze peripheral blood and salivary gland lymphocyte subsets in Sjögren's syndrome. Arthritis Rheum. 1982 Apr;25(4):419–426. doi: 10.1002/art.1780250410. [DOI] [PubMed] [Google Scholar]
  4. Greenspan J. S., Daniels T. E., Talal N., Sylvester R. A. The histopathology of Sjögren's syndrome in labial salivary gland biopsies. Oral Surg Oral Med Oral Pathol. 1974 Feb;37(2):217–229. doi: 10.1016/0030-4220(74)90417-4. [DOI] [PubMed] [Google Scholar]
  5. Hang L., Theofilopoulos A. N., Dixon F. J. A spontaneous rheumatoid arthritis-like disease in MRL/l mice. J Exp Med. 1982 Jun 1;155(6):1690–1701. doi: 10.1084/jem.155.6.1690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hoffman R. W., Alspaugh M. A., Waggie K. S., Durham J. B., Walker S. E. Sjögren's syndrome in MRL/l and MRL/n mice. Arthritis Rheum. 1984 Feb;27(2):157–165. doi: 10.1002/art.1780270206. [DOI] [PubMed] [Google Scholar]
  7. Holmdahl R., Olsson T., Moran T., Klareskog L. In vivo treatment of rats with monoclonal anti-T-cell antibodies. Immunohistochemical and functional analysis in normal rats and in experimental allergic neuritis. Scand J Immunol. 1985 Aug;22(2):157–169. doi: 10.1111/j.1365-3083.1985.tb01868.x. [DOI] [PubMed] [Google Scholar]
  8. 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]
  9. Isenberg D. A., Rowe D., Tookman A., Hopp A., Griffiths M., Paice E., Stewart J., Beverley P. C. An immunohistological study of secondary Sjögren's syndrome. Ann Rheum Dis. 1984 Jun;43(3):470–476. doi: 10.1136/ard.43.3.470. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Jonsson R., Tarkowski A., Bäckman K., Klareskog L. Immunohistochemical characterization of sialadenitis in NZB X NZW F1 mice. Clin Immunol Immunopathol. 1987 Jan;42(1):93–101. doi: 10.1016/0090-1229(87)90176-0. [DOI] [PubMed] [Google Scholar]
  11. Kilpi A., Konttinen Y. T., Malmström M., Bergroth V., Reitamo S., Helve T. Immunocompetent cells in labial salivary glands in secondary Sjögren's syndrome associated with SLE. J Oral Pathol. 1983 Dec;12(6):465–472. doi: 10.1111/j.1600-0714.1983.tb00358.x. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. 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]
  15. Lewis D. E., Giorgi J. V., Warner N. L. Flow cytometry analysis of T cells and continuous T-cell lines from autoimmune MRL/l mice. Nature. 1981 Jan 22;289(5795):298–300. doi: 10.1038/289298a0. [DOI] [PubMed] [Google Scholar]
  16. Lindahl G., Hedfors E., Klareskog L., Forsum U. Epithelial HLA-DR expression and T lymphocyte subsets in salivary glands in Sjögren's syndrome. Clin Exp Immunol. 1985 Sep;61(3):475–482. [PMC free article] [PubMed] [Google Scholar]
  17. MORGAN W. S., CASTLEMAN B. A clinicopathologic study of Mikulicz's disease. Am J Pathol. 1953 May-Jun;29(3):471–503. [PMC free article] [PubMed] [Google Scholar]
  18. 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]
  19. 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]
  20. Phadke K., Fouts R., Parrish J., Baker R. S. Autoreactivity to collagen in a murine lupus model. Arthritis Rheum. 1984 Mar;27(3):313–319. doi: 10.1002/art.1780270311. [DOI] [PubMed] [Google Scholar]
  21. 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]
  22. Prud'Homme G. J., Park C. L., Fieser T. M., Kofler R., Dixon F. J., Theofilopoulos A. N. Identification of a B cell differentiation factor(s) spontaneously produced by proliferating T cells in murine lupus strains of the lpr/lpr genotype. J Exp Med. 1983 Feb 1;157(2):730–742. doi: 10.1084/jem.157.2.730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Simon M. M., Prester M., Nerz G., Kuppers R. C. Quantitative studies on T-cell functions in MRL/MP-Lpr/Lpr mice. I. Frequency analysis of precursor cells of proliferating, cytotoxic, and T-cell growth factor-secreting T lymphocytes reveals an increase in absolute numbers, with a concomitant decrease in percentage of immunocompetent cells. Clin Immunol Immunopathol. 1984 Oct;33(1):39–53. doi: 10.1016/0090-1229(84)90291-5. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. Tarkowski A., Holmdahl R., Rubin K., Klareskog L., Nilsson L. A., Gunnarsson K. Patterns of autoreactivity to collagen type II in autoimmune MRL/l mice. Clin Exp Immunol. 1986 Feb;63(2):441–449. [PMC free article] [PubMed] [Google Scholar]
  27. Theofilopoulos A. N., Dixon F. J. Etiopathogenesis of murine SLE. Immunol Rev. 1981;55:179–216. doi: 10.1111/j.1600-065x.1981.tb00343.x. [DOI] [PubMed] [Google Scholar]
  28. Theofilopoulos A. N., Eisenberg R. A., Bourdon M., Crowell J. S., Jr, Dixon F. J. Distribution of lymphocytes identified by surface markers in murine strains with systemic lupus erythematosus-like syndromes. J Exp Med. 1979 Feb 1;149(2):516–534. doi: 10.1084/jem.149.2.516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]

Articles from Immunology are provided here courtesy of British Society for Immunology

RESOURCES