Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1982 Jan 1;155(1):17–30. doi: 10.1084/jem.155.1.17

Interstitial mononuclear cell populations in renal graft rejection. Identification by monoclonal antibodies in tissue sections

JL Platt, TW LeBien, AF Michael
PMCID: PMC2186571  PMID: 7033436

Abstract

The interstitial mononuclear cell populations of 22 renal grafts with interstitial rejection (IR), 6 grafts with interstitial nephritis without rejection (IN), and 5 kidneys without infiltration (3 donor kidneys, 2 grafts) were identified and quantitated by monoclonal antibodies recognizing T cells (TA-1, OKT3), helper inducer cells (OKT4), cytotoxic/suppressor cells (OKT8), B cells (BA-1), and monocytes and null cells (OKM1). Double-layer fluorochrome enhancement using F(ab’)(2) reagents and nuclear counter staining with ethidium bromide enabled quantitation of the number of positive mononuclear cells, interstitial cells, and total cells on each of 30-55 microscopic fields per tissue section. T cells were the most abundant infiltrating cell in tissues with IR (35 +/- 9.8 percent), significantly higher than that seen in IN (21 +/- 16 percent) or in kidneys without infiltration (5.0 +/- 3.9 percent). The percentage of T cells identified by TA-1 or OKT3 was approximately equivalent to the summation of OKT4 plus OKT8. Although no differences were observed in the percentage of OKT4 cells, the percentage of OKT8 was significantly higher in IR (26 +/- 7.7 percent, P {less than} 10(-4)) than in IN (9.3 +/- 6.2 percent) or in kidneys with normal interstitium (3.0 +/- 2.4 percent). The ratio of OKT8/OKT4-positive T cells in 22 graft tissues with IR (3.2 +/- 1.4) was greater (P {less than} 0.0007) than 6 graft tissues with IN without rejection (0.82 +/- 0.39) and the 5 kidney tissues without interstitial infiltration (0.75 +/- 0.25). There was no significant difference between the groups in the relatively low percentage of interstitial cells identified as B cells reacting with BA-1 or containing S(IgD,M). The percentage of interstitial cells recognized by OKM1 was similar in rejection and interstitial nephritis, with both being greater than controls (P {less than} 0.02). The relative numbers of blood mononuclear cells identified by the monoclonal antibodies was generally not predictive of the proportions present in kidney tissue, although OKT4-positive blood cells were less numerous and OKMI+ blood cells were more numerous than in controls (P {less than} 0.002). Quantitative analysis of identifiable interstitial cells in graft rejection reveals that most infiltrating cells are T cells, the greater proportion of which are recognized by OKT8. OKT8-positive cells may play an important role in mediating renal graft rejection.

Full Text

The Full Text of this article is available as a PDF (1.2 MB).

Selected References

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

  1. Abramson C. S., Kersey J. H., LeBien T. W. A monoclonal antibody (BA-1) reactive with cells of human B lymphocyte lineage. J Immunol. 1981 Jan;126(1):83–88. [PubMed] [Google Scholar]
  2. Ault K. A., Towle M. Human B lymphocyte subsets. I. IgG-bearing B cell response to pokeweed mitogen. J Exp Med. 1981 Feb 1;153(2):339–351. doi: 10.1084/jem.153.2.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bhan A. K., Reinherz E. L., Poppema S., McCluskey R. T., Schlossman S. F. Location of T cell and major histocompatibility complex antigens in the human thymus. J Exp Med. 1980 Oct 1;152(4):771–782. doi: 10.1084/jem.152.4.771. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Breard J., Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. A monoclonal antibody reactive with human peripheral blood monocytes. J Immunol. 1980 Apr;124(4):1943–1948. [PubMed] [Google Scholar]
  5. Busch G. J., Schamberg J. F., Moretz R. C., Strom T. B., Tilney N. L., Carpenter C. B. T and B cell patterns in irreversibly rejected human renal allografts. Correlation of morphology with surface markers and cytotoxic capacity of the isolated lymphoid infiltrates. Lab Invest. 1976 Sep;35(3):272–280. [PubMed] [Google Scholar]
  6. Cosimi A. B., Colvin R. B., Burton R. C., Rubin R. H., Goldstein G., Kung P. C., Hansen W. P., Delmonico F. L., Russell P. S. Use of monoclonal antibodies to T-cell subsets for immunologic monitoring and treatment in recipients of renal allografts. N Engl J Med. 1981 Aug 6;305(6):308–314. doi: 10.1056/NEJM198108063050603. [DOI] [PubMed] [Google Scholar]
  7. De Waele M., Thielemans C., Van Camp B. K. Characterization of immunoregulatory T cells in EBV-induced infectious mononucleosis by monoclonal antibodies. N Engl J Med. 1981 Feb 19;304(8):460–462. doi: 10.1056/NEJM198102193040804. [DOI] [PubMed] [Google Scholar]
  8. Fossum S., Rolstad B., Tjernshaugen H. Selective loss of S-phase cells when making cell suspensions from lymphoid tissue. Cell Immunol. 1979 Nov;48(1):149–154. doi: 10.1016/0008-8749(79)90107-2. [DOI] [PubMed] [Google Scholar]
  9. Franklin W. A., Locker J. D. Ethidium bromide: a nucleic acid stain for tissue section. J Histochem Cytochem. 1981 Apr;29(4):572–576. doi: 10.1177/29.4.6166660. [DOI] [PubMed] [Google Scholar]
  10. Haynes B. F., Metzgar R. S., Minna J. D., Bunn P. A. Phenotypic characterization of cutaneous T-cell lymphoma. Use of monoclonal antibodies to compare with other malignant T cells. N Engl J Med. 1981 May 28;304(22):1319–1323. doi: 10.1056/NEJM198105283042202. [DOI] [PubMed] [Google Scholar]
  11. Husby G., Tung K. S., Williams R. C., Jr Characterization of renal tissue lymphocytes in patients with interstitial nephritis. Am J Med. 1981 Jan;70(1):31–38. doi: 10.1016/0002-9343(81)90408-3. [DOI] [PubMed] [Google Scholar]
  12. Janossy G., Tidman N., Papageorgiou E. S., Kung P. C., Goldstein G. Distribution of t lymphocyte subsets in the human bone marrow and thymus: an analysis with monoclonal antibodies. J Immunol. 1981 Apr;126(4):1608–1613. [PubMed] [Google Scholar]
  13. Kersey J. H., LeBien T. W., Abramson C. S., Newman R., Sutherland R., Greaves M. P-24: a human leukemia-associated and lymphohemopoietic progenitor cell surface structure identified with monoclonal antibody. J Exp Med. 1981 Mar 1;153(3):726–731. doi: 10.1084/jem.153.3.726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kung P., Goldstein G., Reinherz E. L., Schlossman S. F. Monoclonal antibodies defining distinctive human T cell surface antigens. Science. 1979 Oct 19;206(4416):347–349. doi: 10.1126/science.314668. [DOI] [PubMed] [Google Scholar]
  15. LeBien T. W., Kersey J. H. A monoclonal antibody (TA-1) reactive with human T lymphocytes and monocytes. J Immunol. 1980 Nov;125(5):2208–2214. [PubMed] [Google Scholar]
  16. McPhaul J. J., Jr, Stastny P., Freeman R. B. Specificities of antibodies eluted from human cadaveric renal allografts. Multiple mechanisms of renal allograft injury. J Clin Invest. 1981 May;67(5):1405–1414. doi: 10.1172/JCI110169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Poppema S., Bhan A. K., Reinherz E. L., McCluskey R. T., Schlossman S. F. Distribution of T cell subsets in human lymph nodes. J Exp Med. 1981 Jan 1;153(1):30–41. doi: 10.1084/jem.153.1.30. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Potter M. Immunoglobulin-producing tumors and myeloma proteins of mice. Physiol Rev. 1972 Jul;52(3):631–719. doi: 10.1152/physrev.1972.52.3.631. [DOI] [PubMed] [Google Scholar]
  19. Reinherz E. L., Kung P. C., Goldstein G., Levey R. H., Schlossman S. F. Discrete stages of human intrathymic differentiation: analysis of normal thymocytes and leukemic lymphoblasts of T-cell lineage. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1588–1592. doi: 10.1073/pnas.77.3.1588. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Reinherz E. L., Kung P. C., Goldstein G., Schlossman S. F. Separation of functional subsets of human T cells by a monoclonal antibody. Proc Natl Acad Sci U S A. 1979 Aug;76(8):4061–4065. doi: 10.1073/pnas.76.8.4061. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Stashenko P., Nadler L. M., Hardy R., Schlossman S. F. Expression of cell surface markers after human B lymphocyte activation. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3848–3852. doi: 10.1073/pnas.78.6.3848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Strom T. B., Tilney N. L., Carpenter C. B., Busch G. J. Identity and cytotoxic capacity of cells infiltrating renal allografts. N Engl J Med. 1975 Jun 12;292(24):1257–1263. doi: 10.1056/NEJM197506122922402. [DOI] [PubMed] [Google Scholar]
  23. Tilney N. L., Garovoy M. R., Busch G. J., Strom T. B., Graves M. J., Carpenter C. B. Rejected human renal allografts: recovery and characteristics of infiltrating cells and antibody. Transplantation. 1979 Nov;28(5):421–426. doi: 10.1097/00007890-197911000-00015. [DOI] [PubMed] [Google Scholar]
  24. Tubbs R. R., Sheibani K., Weiss R. A., Sebek B. A., Deodhar S. D. Tissue immunomicroscopic evaluation of monoclonality of B-cell lymphomas: comparison with cell suspension studies. Am J Clin Pathol. 1981 Jul;76(1):24–28. doi: 10.1093/ajcp/76.1.24. [DOI] [PubMed] [Google Scholar]
  25. Winchester R. J., Fu S. M., Hoffman T., Kunkel H. G. IgG on lymphocyte surfaces; technical problems and the significance of a third cell population. J Immunol. 1975 Apr;114(4):1210–1212. [PubMed] [Google Scholar]
  26. von Willebrand E., Häyry P. Composition and in vitro cytotoxicity of cellular infiltrates in rejecting human kidney allografts. Cell Immunol. 1978 Dec;41(2):358–372. doi: 10.1016/0008-8749(78)90233-2. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES