Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1984 May;73(5):1263–1276. doi: 10.1172/JCI111328

New avian model of experimental glomerulonephritis consistent with mediation by cellular immunity. Nonhumorally mediated glomerulonephritis in chickens.

W K Bolton, F L Tucker, B C Sturgill
PMCID: PMC425147  PMID: 6585368

Abstract

The present study examined the role of cell-mediated immunity (CMI) in the production of experimental autoimmune glomerulonephritis (EAG) in chickens deficient in humorally mediated immunity (HMI). Cyclophosphamide bursectomized (Bsx) and normal control chickens were used. Bsx chickens were used only if they had severe depression of HMI, which was evidenced by marked reduction in bursal weights (0.89 +/- 0.23 vs. 2.92 +/- 0.9 g), decreased serum IgG to less than or equal to 10% of normal, and total lack of HMI to immunization with sheep red blood cells. EAG was produced by immunizing chickens with bovine glomerular basement membrane (GBM) in complete Freund's adjuvant. CMI manifested by wattle thickness increments to PPD was not different, 3.89 +/- 0.45 mm for Bsx compared with 3.73 +/- 0.75 mm for controls. No circulating antibodies to GBM developed in 68% of Bsx chickens, and the anti-GBM titers were less than 1:312 in those Bsx chickens positive for antibody compared with greater than 2,000 for controls. GBM deposits of IgG by fluorescence were much decreased, 0.53 +/- 0.16 compared with 2.19 +/- 0.32 for controls, and were absent in 64% of Bsx chickens. Nonetheless, proliferative nephritis with crescents was present and was even more severe in Bsx chickens than in controls, with glomerular sizes of 20.8 +/- 0.6 U for Bsx-GBM, 19.8 +/- 1.2 for control-GBM, 14.9 +/- 1.5 for Bsx, and 13.6 +/- 0.8 for normal chickens. Nephritic eluates did not produce disease in normal chickens, while administration of sensitized cells with [H3]thymidine to naive birds was associated with increased mesangial grain counts by autoradiography. These findings suggest that CMI plays a major role in the pathogenesis of EAG in chickens in the absence of HMI. By implication, CMI may be crucial in the development of other types of glomerulonephritis as well.

Full text

PDF
1276

Images in this article

1267Image
on p.1267
1267Image
on p.1267
1269Image
on p.1269
1273Image
on p.1273
1273Image
on p.1273
1273Image
on p.1273

Selected References

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

  1. Atkins R. C., Glasgow E. F., Holdsworth S. R., Thomson N. M., Hancock W. W. Tissue culture of isolated glomeruli from patients with glomerulonephritis. Kidney Int. 1980 Apr;17(4):515–527. doi: 10.1038/ki.1980.60. [DOI] [PubMed] [Google Scholar]
  2. Atkins R. C., Holdsworth S. R., Glasgow E. F., Matthews F. E. The macrophagen in human rapidly progressive glomerulonephritis. Lancet. 1976 Apr 17;1(7964):830–832. doi: 10.1016/s0140-6736(76)90480-3. [DOI] [PubMed] [Google Scholar]
  3. Bendixen G. Organ-specific inhibition of the in vitro migration of leucocytes in human glomerulonephritis. Acta Med Scand. 1968 Jul-Aug;184(1-2):99–103. doi: 10.1111/j.0954-6820.1968.tb02428.x. [DOI] [PubMed] [Google Scholar]
  4. Bhan A. K., Schneeberger E. E., Collins A. B., McCluskey R. T. Evidence for a pathogenic role of a cell-mediated immune mechanism in experimental glomerulonephritis. J Exp Med. 1978 Jul 1;148(1):246–260. doi: 10.1084/jem.148.1.246. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bolton W. K., Atuk N. O., Sturgill B. C. Nephrotoxic nephritis in rabbits. The role of the sympathetic nervous system. Am J Pathol. 1978 Mar;90(3):689–700. [PMC free article] [PubMed] [Google Scholar]
  6. Bolton W. K., Benton F. R., Lobo P. I. Requirement of functional T-cells in the production of autoimmune glomerulotubular nephropathy in mice. Clin Exp Immunol. 1978 Sep;33(3):474–477. [PMC free article] [PubMed] [Google Scholar]
  7. Bolton W. K., Benton F. R., Maclay J. G., Sturgill B. C. Spontaneous glomerular sclerosis in aging Sprague-Dawley rats. I. Lesions associated with mesangial IgM deposits. Am J Pathol. 1976 Nov;85(2):277–302. [PMC free article] [PubMed] [Google Scholar]
  8. Bolton W. K., Benton F. R., Sturgill B. C. Autoimmune glomerulotubular nephropathy in mice. Clin Exp Immunol. 1978 Sep;33(3):463–473. [PMC free article] [PubMed] [Google Scholar]
  9. Bolton W. K., Couser W. G. Intravenous pulse methylprednisolone therapy of acute crescentic rapidly progressive glomerulonephritis. Am J Med. 1979 Mar;66(3):495–502. doi: 10.1016/0002-9343(79)91081-7. [DOI] [PubMed] [Google Scholar]
  10. Bolton W. K., Mesnard R. M. New technique of kidney tissue processing for immunofluorescence microscopy: formol sucrose/gum sucrose/paraffin. Lab Invest. 1982 Aug;47(2):206–213. [PubMed] [Google Scholar]
  11. Bolton W. K., Spargo B. A., Lewis E. J. Chronic autologous immune complex glomerulopathy: effect of cyproheptadine. J Lab Clin Med. 1974 May;83(5):695–704. [PubMed] [Google Scholar]
  12. Bolton W. K., Sturgill B. C. Bovine serum albumin chronic serum sickness nephropathy in rats. Br J Exp Pathol. 1978 Apr;59(2):167–177. [PMC free article] [PubMed] [Google Scholar]
  13. Bolton W. K., Tucker F. L., Sturgill B. C. Experimental autoimmune glomerulonephritis in chickens. J Clin Lab Immunol. 1980 May;3(3):179–184. [PubMed] [Google Scholar]
  14. Bradfield J. W., Cattell V. The mesangial cell in glomerulonephritis. I. Mechanisms of hypercellularity in experimental immune complex glomerulonephritis. Lab Invest. 1977 May;36(5):481–486. [PubMed] [Google Scholar]
  15. Brune K., Spitznagel J. K. Peroxidaseless chicken leukocytes: isolation and characterization of antibacterial granules. J Infect Dis. 1973 Jan;127(1):84–94. doi: 10.1093/infdis/127.1.84. [DOI] [PubMed] [Google Scholar]
  16. Cattell V., Jamieson S. W. The origin of glomerular crescents in experimental nephrotoxic serum nephritis in the rabbit. Lab Invest. 1978 Dec;39(6):584–590. [PubMed] [Google Scholar]
  17. Dixon F. J. What are sensitized cells doing in glomerulonephritis? N Engl J Med. 1970 Sep 3;283(10):536–537. doi: 10.1056/NEJM197009032831011. [DOI] [PubMed] [Google Scholar]
  18. Dubois C. H., Foidart J. B., Hautier M. B., Dechenne C. A., Lemaire M. J., Mahieu P. R. Proliferative glomerulonephritis in rats: evidence that mononuclear phagocytes infiltrating the glomeruli stimulate the proliferation of endothelial and mesangial cells. Eur J Clin Invest. 1981 Apr;11(2 Suppl 1):91–104. doi: 10.1111/j.1365-2362.1981.tb02045.x. [DOI] [PubMed] [Google Scholar]
  19. Fillit H. M., Read S. E., Sherman R. L., Zabriskie J. B., Van de Rijn I. Cellular reactivity to altered glomerular basement membrane in glomerulonephritis. N Engl J Med. 1978 Apr 20;298(16):861–868. doi: 10.1056/NEJM197804202981601. [DOI] [PubMed] [Google Scholar]
  20. Hirota Y., Bito Y. The role of the thymus for maturation of transferred bursa cells into immunocompetent B cells in chickens treated with cyclophosphamide. Immunology. 1978 Dec;35(6):889–899. [PMC free article] [PubMed] [Google Scholar]
  21. Holdsworth S. R., Neale T. J., Wilson C. B. Abrogation of macrophage-dependent injury in experimental glomerulonephritis in the rabbit. Use of an antimacrophage serum. J Clin Invest. 1981 Sep;68(3):686–698. doi: 10.1172/JCI110304. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Holdsworth S. R., Neale T. J., Wilson C. B. The participation of macrophages and monocytes in experimental immune complex glomerulonephritis. Clin Immunol Immunopathol. 1980 Mar;15(3):510–524. doi: 10.1016/0090-1229(80)90063-x. [DOI] [PubMed] [Google Scholar]
  23. Holdsworth S. R., Thomson N. M., Glasgow E. F., Dowling J. P., Atkins R. C. Tissue culture of isolated glomeruli in experimental crescentic glomerulonephritis. J Exp Med. 1978 Jan 1;147(1):98–109. doi: 10.1084/jem.147.1.98. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Hunsicker L. G., Shearer T. P., Plattner S. B., Weisenburger D. The role of monocytes in serum sickness nephritis. J Exp Med. 1979 Sep 19;150(3):413–425. doi: 10.1084/jem.150.3.413. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Janas-Boratyńska M. Cell-mediated hypersensitvity in glomerulonephritis. Arch Immunol Ther Exp (Warsz) 1979;27(1-2):15–27. [PubMed] [Google Scholar]
  26. Kreisberg J. I., Wayne D. B., Karnovsky M. J. Rapid and focal loss of negative charge associated with mononuclear cell infiltration early in nephrotoxic serum nephritis. Kidney Int. 1979 Sep;16(3):290–300. doi: 10.1038/ki.1979.131. [DOI] [PubMed] [Google Scholar]
  27. Krejcí J., Karakoz I., Pekárek J., Hraba T., Hála K. Differences between inbred lines of chickens in development of tuberculin hypersensitivity. Immunology. 1974 Jul;27(1):133–136. [PMC free article] [PubMed] [Google Scholar]
  28. Lavelle K. J., Durland B. D., Yum M. N. The effect of antimacrophage antiserum on immune complex glomerulonephritis. J Lab Clin Med. 1981 Aug;98(2):195–205. [PubMed] [Google Scholar]
  29. Lerman S. P., Weidanz W. P. The effect of cyclophosphamide on the ontogeny of the humoral immune response in chickens. J Immunol. 1970 Sep;105(3):614–619. [PubMed] [Google Scholar]
  30. Lerner R. A., Dixon F. J. Transfer of ovine experimental allergic glomerulonephritis (EAG) with serum. J Exp Med. 1966 Sep 1;124(3):431–442. doi: 10.1084/jem.124.3.431. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Linna T. J., Frommel D., Good R. A. Effects of early cyclophosphamide treatment on the development of lymphoid organs and immunological functions in the chickens. Int Arch Allergy Appl Immunol. 1972;42(1):20–39. doi: 10.1159/000230590. [DOI] [PubMed] [Google Scholar]
  32. Macanovic M., Evans D. J., Peters D. K. Alllergic response to glomerular basement membrane in patients with glomerulonephritis. Lancet. 1972 Jul 29;2(7770):207–210. doi: 10.1016/s0140-6736(72)91637-6. [DOI] [PubMed] [Google Scholar]
  33. Magil A. B., Wadsworth L. D., Loewen M. Monocytes and human renal glomerular disease: a quantitative evaluation. Lab Invest. 1981 Jan;44(1):27–33. [PubMed] [Google Scholar]
  34. Mahieu P., Dardenne M., Bach J. F. Detection of humoral and cell-mediated immunity to kidney basement membranes in human renal diseases. Am J Med. 1972 Aug;53(2):185–192. doi: 10.1016/0002-9343(72)90128-3. [DOI] [PubMed] [Google Scholar]
  35. Min K. W., Györkey F., Györkey P., Yium J. J., Eknoyan G. The morphogenesis of glomerular crescents in rapidly progressive glomerulonephritis. Kidney Int. 1974 Jan;5(1):47–56. doi: 10.1038/ki.1974.6. [DOI] [PubMed] [Google Scholar]
  36. Mollo F., Campobasso O., Canese M. G., Monga G., Palestro G. Glomerular cell proliferation in human and experimental glomerulonephritis. Light- and electron-microscopical, and autoradiographic observations. Nephron. 1977;18(2):101–108. doi: 10.1159/000180783. [DOI] [PubMed] [Google Scholar]
  37. Monga G., Mazzucco G., di Belgiojoso G. B., Busnach G. The presence and possible role of monocyte infiltration in human chronic proliferative glomerulonephritides. Light microscopic, immunofluorescence, and histochemical correlations. Am J Pathol. 1979 Feb;94(2):271–284. [PMC free article] [PubMed] [Google Scholar]
  38. Morita T., Suzuki Y., Churg J. Structure and development of the glomerular crescent. Am J Pathol. 1973 Sep;72(3):349–368. [PMC free article] [PubMed] [Google Scholar]
  39. Mueller J., Brun del Re G., Buerki H., Keller H. U., Hess M. W., Cottier H. Nonspecific acid esterase activity: a criterion for differentiation of T and B lymphocytes in mouse lymph nodes. Eur J Immunol. 1975 Apr;5(4):270–274. doi: 10.1002/eji.1830050411. [DOI] [PubMed] [Google Scholar]
  40. Nielsen K. H., White R. G. Effect of host decomplementation on homeostasis of antibody production in fowl. Nature. 1974 Jul 19;250(463):234–236. doi: 10.1038/250234a0. [DOI] [PubMed] [Google Scholar]
  41. Polverini P. J., Cotran P. S., Gimbrone M. A., Jr, Unanue E. R. Activated macrophages induce vascular proliferation. Nature. 1977 Oct 27;269(5631):804–806. doi: 10.1038/269804a0. [DOI] [PubMed] [Google Scholar]
  42. Rocklin R. E., Lewis E. J., David J. R. In vitro evidence for cellular hypersensitivity to glomerular-basement-membrane antigens in human glomerulonephritis. N Engl J Med. 1970 Sep 3;283(10):497–501. doi: 10.1056/NEJM197009032831001. [DOI] [PubMed] [Google Scholar]
  43. Sano M. Participation of monocytes in glomerulonephritis in acute serum sickness of rabbit. Acta Pathol Jpn. 1976 Jul;26(4):423–433. doi: 10.1111/j.1440-1827.1976.tb00500.x. [DOI] [PubMed] [Google Scholar]
  44. Schiffer M. S., Michael A. F. Renal cell turnover studied by Y chromosome (Y body) staining of the transplanted human kidney. J Lab Clin Med. 1978 Dec;92(6):841–848. [PubMed] [Google Scholar]
  45. Schreiner G. F., Cotran R. S., Pardo V., Unanue E. R. A mononuclear cell component in experimental immunological glomerulonephritis. J Exp Med. 1978 Feb 1;147(2):369–384. doi: 10.1084/jem.147.2.369. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Shigematsu H., Kobayashi Y. Accelerated serum sickness in the rabbit. II. Glomerular ultrastructural lesions in transient proliferative and progressive disorganizing glomerulonephritis. Virchows Arch A Pathol Anat Histol. 1976 Mar 5;369(4):269–282. doi: 10.1007/BF00432449. [DOI] [PubMed] [Google Scholar]
  47. Stilmant M. M., Bolton W. K., Sturgill B. C., Schmitt G. W., Couser W. G. Crescentic glomerulonephritis without immune deposits: clinicopathologic features. Kidney Int. 1979 Feb;15(2):184–195. doi: 10.1038/ki.1979.24. [DOI] [PubMed] [Google Scholar]
  48. Striker G. E., Mannik M., Tung M. Y. Role of marrow-derived monocytes and mesangial cells in removal of immune complexes from renal glomeruli. J Exp Med. 1979 Jan 1;149(1):127–136. doi: 10.1084/jem.149.1.127. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Thomson N. M., Holdsworth S. R., Glasgow E. F., Atkins R. C. The macrophage in the development of experimental crescentic glomerulonephritis. Studies using tissue culture and electron microscopy. Am J Pathol. 1979 Feb;94(2):223–240. [PMC free article] [PubMed] [Google Scholar]
  50. UNANUE E. R., DIXON F. J. EXPERIMENTAL GLOMERULONEPHRITIS. V. STUDIES ON THE INTERACTION OF NEPHROTOXIC ANTIBODIES WITH TISSUE OF THE RAT. J Exp Med. 1965 May 1;121:697–714. doi: 10.1084/jem.121.5.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Zabriskie J. B., Lewshenia R., Möller G., Wehle B., Falk R. E. Lymphocytic responses to streptococcal antigens in glomerulonephritic patients. Science. 1970 May 29;168(3935):1105–1108. doi: 10.1126/science.168.3935.1105. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES