Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1986 Jan;63(1):218–227.

Immune defects in chronic renal impairment: evidence for defective regulation of lymphocyte response by macrophages from patients with chronic renal impairment on haemodialysis.

N D Tsakolos, T C Theoharides, E D Hendler, J Goffinet, J M Dwyer, R L Whisler, P W Askenase
PMCID: PMC1577352  PMID: 2937581

Abstract

Cellular mechanisms contributing to impaired lymphocyte proliferative responses in chronic renal impairment (CRI) were investigated using peripheral blood mononuclear cells (PBMC) from 25 patients receiving haemodialysis. Impaired T cell proliferative responses to phytohaemagglutinin were demonstrated. The hyporeactive PBMC from patients with CRI suppressed the responses of PBMC from normals to a greater degree than did control PBMC. This immunosuppression was reversed significantly by depleting adherent monocytes (M phi). To further determine if these impairments might be critically dependent on cell-cell contact, M phi from an additional 10 patients on haemodialysis were examined for ability to support B and T cell colony formation in semi-solid cultures stimulated by Staphylococcus protein A (SpA). When compared to normal controls, significantly fewer B and T cell colonies were observed with M phi from CRI patients than when autologous M phi were used. Also, T cells from patients were significantly less effective than controls in supporting B cell colony growth. Decreased T and B cell colony responses in patients were not due to a primary abnormality of these cells, since allogeneic mixing experiments showed that B and T cells from patients were able to form a sufficient number of colonies when control M phi or T cells from normals were used as accessory and helper cells. These findings suggest that although M phi-mediated suppressor activity is an important mechanism contributing to impaired lymphocyte responsiveness in patients with chronic renal impairment on haemodialysis, additional or related abnormalities in M phi 'accessory' function may also exist.

Full text

PDF
219

Selected References

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

  1. Alevy Y. G., Slavin R. G., Hutcheson P. Immune response in experimentally induced uremia. I. Suppression of mitogen responses by adherent cells in chronic uremia. Clin Immunol Immunopathol. 1981 Apr;19(1):8–18. doi: 10.1016/0090-1229(81)90043-x. [DOI] [PubMed] [Google Scholar]
  2. Alevy Y. G., Slavin R. G. Immune response in experimentally induced uremia. II. Suppression of PHA response in uremia is mediated by an adherent, Ia-negative and indomethacin-insensitive suppressor cell. J Immunol. 1981 May;126(5):2007–2010. [PubMed] [Google Scholar]
  3. Beer D. J., Osband M. E., McCaffrey R. P., Soter N. A., Rocklin R. E. Abnormal histamine-induced suppressor-cell function in atopic subjects. N Engl J Med. 1982 Feb 25;306(8):454–458. doi: 10.1056/NEJM198202253060804. [DOI] [PubMed] [Google Scholar]
  4. Bobak D., Whisler R. Human B lymphocyte colony responses. I. General characteristics and modulation by monocytes. J Immunol. 1980 Dec;125(6):2764–2769. [PubMed] [Google Scholar]
  5. Bresnihan B., Jasin H. E. Suppressor function of peripheral blood mononuclear cells in normal individuals and in patients with systemic lupus erythematosus. J Clin Invest. 1977 Jan;59(1):106–116. doi: 10.1172/JCI108607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Dobbelstein H. Immune system to uremia. Nephron. 1976;17(6):409–414. doi: 10.1159/000180749. [DOI] [PubMed] [Google Scholar]
  7. Dwyer J. M., Johnson C. The regulation of T cell responses by spontaneously active suppressor cells. Clin Exp Immunol. 1982 Nov;50(2):406–415. [PMC free article] [PubMed] [Google Scholar]
  8. Dwyer J. M., Johnson C. The use of concanavalin A to study the immunoregulation of human T cells. Clin Exp Immunol. 1981 Nov;46(2):237–249. [PMC free article] [PubMed] [Google Scholar]
  9. Elves M. W., Israëls M. C., Collinge M. An assessment of the mixed leucocyte reaction in renal failure. Lancet. 1966 Mar 26;1(7439):682–685. doi: 10.1016/s0140-6736(66)91628-x. [DOI] [PubMed] [Google Scholar]
  10. Katz P., Fauci A. S. Inhibition of polyclonal B-cell activation by suppressor monocytes in patients with sarcoidosis. Clin Exp Immunol. 1978 Jun;32(3):554–562. [PMC free article] [PubMed] [Google Scholar]
  11. Kumagai S., Sredni B., House S., Steinberg A. D., Green I. Defective regulation of B lymphocyte colony formation in patients with systemic lupus erythematosus. J Immunol. 1982 Jan;128(1):258–262. [PubMed] [Google Scholar]
  12. Markenson J. A., Morgan J. W., Lockshin M. D., Joachim C., Winfield J. B. Responses of fractionated cells from patients with systemic lupus erythematosus and normals to plant mitogen: evidence for a suppressor population of monocytes. Proc Soc Exp Biol Med. 1978 May;158(1):5–9. doi: 10.3181/00379727-158-40127. [DOI] [PubMed] [Google Scholar]
  13. Muraguchi A., Kishimoto T., Kuritani T., Yamamura Y. In vitro immune response of human peripheral lymphocytes. VII. Effect of anti-mu and anti-delta antibodies on B colony formation and detection of abnormal B cells in patients with juvenile rheumatoid arthritis. J Immunol. 1980 Dec;125(6):2638–2642. [PubMed] [Google Scholar]
  14. Newberry W. M., Sanford J. P. Defective cellular immunity in renal failure: depression of reactivity of lymphocytes to phytohemagglutinin by renal failure serum. J Clin Invest. 1971 Jun;50(6):1262–1271. doi: 10.1172/JCI106604. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Quadracci L. J., Ringdén O., Krzymanski M. The effect of uremia and transplantation on lymphocyte subpopulations. Kidney Int. 1976 Aug;10(2):179–184. doi: 10.1038/ki.1976.93. [DOI] [PubMed] [Google Scholar]
  16. RIIS P., STOUGAARD J. The peripheral blood leukocytes in chronic renal insufficiency. Dan Med Bull. 1959 May;6(3):85–90. [PubMed] [Google Scholar]
  17. Radnay J., Goldman I., Rozenszajn L. A. Growth of human B-lymphocyte colonies in vitro. Nature. 1979 Mar 22;278(5702):351–353. doi: 10.1038/278351a0. [DOI] [PubMed] [Google Scholar]
  18. Raskova J., Morrison A. B. A decrease in cell-mediated immunity in uremia associated with an increase in activity of suppressor cells. Am J Pathol. 1976 Jul;84(1):1–10. [PMC free article] [PubMed] [Google Scholar]
  19. Sakane T., Green I. Protein A from Staphylococcus aureus-a mitogen for human T lymphocytes and B lymphocytes but not L lymphocytes. J Immunol. 1978 Jan;120(1):302–311. [PubMed] [Google Scholar]
  20. Scala G., Oppenheim J. J. Antigen presentation by human monocytes: evidence for stimulant processing and requirement for interleukin 1. J Immunol. 1983 Sep;131(3):1160–1166. [PubMed] [Google Scholar]
  21. Schechter G. P., Soehnlen F. Monocyte-mediated inhibition of lymphocyte blastogenesis in Hodgkin disease. Blood. 1978 Aug;52(2):261–271. [PubMed] [Google Scholar]
  22. Shibasaki M., Nemoto H., Suzuki S., Kuroume T. Induction of lymphocyte colony formation in vitro by protein A. J Immunol. 1978 Dec;121(6):2278–2281. [PubMed] [Google Scholar]
  23. Slavin R. G., Fitch C. D. Inhibition of lymphocyte transformation by guanidinosuccinic acid, a surplus metabolite in uremia. Experientia. 1971;27(11):1340–1341. doi: 10.1007/BF02136727. [DOI] [PubMed] [Google Scholar]
  24. Stobo J. D. Immunosuppression in man: suppression by macrophages can be mediated by interactions with regulatory T cells. J Immunol. 1977 Sep;119(3):918–924. [PubMed] [Google Scholar]
  25. Touraine J. L., Touraine F., Revillard J. P., Brochier J., Traeger J. T-lymphocytes and serum inhibitors of cell-mediated immunity in renal insufficiency. Nephron. 1975;14(2):195–208. doi: 10.1159/000180448. [DOI] [PubMed] [Google Scholar]
  26. Tsakalos N. D., Lachman L. B., Newhouse Y. G., Whisler R. L. Lipopolysaccharide (LPS) modulation of human monocyte accessory cell function in promoting T-cell colonies: inability of LPS and IL-1 to abrogate the need for monocytes with high HLA-DR expression. Cell Immunol. 1984 Feb;83(2):229–241. doi: 10.1016/0008-8749(84)90302-2. [DOI] [PubMed] [Google Scholar]
  27. Whisler R. L., Bobak D. A., Newhouse Y. G. Human B lymphocyte colony responses. II. The role of T cells in the enhancement of colony growth. J Immunol. 1981 Nov;127(5):1758–1762. [PubMed] [Google Scholar]
  28. Zembala M., Mytar B., Popiela T., Asherson G. L. Depressed in vitro peripheral blood lymphocyte response to mitogens in cancer patients: the role of suppressor cells. Int J Cancer. 1977 May 15;19(5):605–613. doi: 10.1002/ijc.2910190503. [DOI] [PubMed] [Google Scholar]

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

RESOURCES