Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1986 Apr;64(1):125–135.

Human immune responses in vivo to protein (KLH) and polysaccharide (DNP-Ficoll) neoantigens: normal subjects compared with bone marrow transplant patients on cyclosporine.

P L Amlot, A E Hayes, D Gray, E C Gordon-Smith, J H Humphrey
PMCID: PMC1542141  PMID: 2426019

Abstract

Thymus-independent (TI) and thymus-dependent (TD) primary immune responses were measured in 67 controls and 13 bone marrow transplant (BMT) recipients treated with cyclosporine (CSP) by immunizing with a synthetic antigen (DNP-Ficoll) and keyhole limpet haemocyanin (KLH). DNP-Ficoll induced similar TI antibody responses in controls and BMT recipients except that antibody levels declined much more rapidly in BMT recipients. The IgM and IgG antibodies induced by DNP-Ficoll only recognized the DNP epitope and not the Ficoll carrier. Both IgM and IgG classes of antibody showed similar TI behaviour upon immunization and re-immunization. The antibodies to DNP-Ficoll were overwhelmingly of the IgG1 subclass. The TD response to KLH evoked both delayed hypersensitivity (DH) and antibody production. DH developed at the site of immunization in 68% of controls and in 88% upon subsequent challenge with KLH. None of the BMT recipients on CSP developed DH. KLH antibody arose in 88% of controls but in only one BMT recipient on CSP. Eight BMT recipients were re-immunized with KLH 2-6 weeks after stopping CSP and only one made primary DH and antibody responses, arguing that CSP inhibited priming as well as any detectable response to KLH. The immunization procedure described has proved a sensitive and comprehensive method of quantitating human immune responses in vivo and is readily adaptable for in vitro studies.

Full text

PDF
125

Selected References

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

  1. Amlot P. L., Grennan D., Humphrey J. H. Splenic dependence of the antibody response to thymus-independent (TI-2) antigens. Eur J Immunol. 1985 May;15(5):508–512. doi: 10.1002/eji.1830150516. [DOI] [PubMed] [Google Scholar]
  2. Amlot P. L., Hayes A. E. Impaired human antibody response to the thymus-independent antigen, DNP-Ficoll, after splenectomy. Implications for post-splenectomy infections. Lancet. 1985 May 4;1(8436):1008–1011. doi: 10.1016/s0140-6736(85)91613-7. [DOI] [PubMed] [Google Scholar]
  3. Benedict A. A. Sensitivity of passive haemagglutination for assay of 7S and 19S antibodies in primary rabbit anti-bovine serum albumin sera. Nature. 1965 Jun 26;206(991):1368–1369. doi: 10.1038/2061368b0. [DOI] [PubMed] [Google Scholar]
  4. Catalona W. J., Taylor P. T., Rabson A. S., Chretien P. B. A method for dinitrochlorobenzene contact sensitization. A clinicopathological study. N Engl J Med. 1972 Feb 24;286(8):399–402. doi: 10.1056/NEJM197202242860804. [DOI] [PubMed] [Google Scholar]
  5. Curtis J. E., Hersh E. M., Harris J. E., McBride C., Freireich E. J. The human primary immune response to keyhole limpet haemocyanin: interrelationships of delayed hypersensitivity, antibody response and in vitro blast transformation. Clin Exp Immunol. 1970 Apr;6(4):473–491. [PMC free article] [PubMed] [Google Scholar]
  6. Curtis J. E., Hersh E. M. The human secondary immune response to Keyhole limpet haemocyanin. Clin Exp Immunol. 1972 Jan;10(1):171–177. [PMC free article] [PubMed] [Google Scholar]
  7. HUNTER W. M., GREENWOOD F. C. Preparation of iodine-131 labelled human growth hormone of high specific activity. Nature. 1962 May 5;194:495–496. doi: 10.1038/194495a0. [DOI] [PubMed] [Google Scholar]
  8. Herscowitz H. B., Harold W. W., Stavitsky A. B. Immunochemical and immunogenic properties of a purified keyhold limpet haemocyanin. Immunology. 1972 Jan;22(1):51–61. [PMC free article] [PubMed] [Google Scholar]
  9. Humphrey J. H. Tolerogenic or immunogenic activity of hapten-conjugated polysaccharides correlated with cellular localization. Eur J Immunol. 1981 Mar;11(3):212–220. doi: 10.1002/eji.1830110310. [DOI] [PubMed] [Google Scholar]
  10. Jones J. M., Amsbaugh D. F., Stashak P. W., Prescott B., Baker P. J., Alling D. W. Kinetics of the antibody response to type III pneumococcal polysaccharide. I. Evidence that suppressor cells function by inhibiting the recruitment and proliferation of antibody-producing cells. J Immunol. 1976 Mar;116(3):647–656. [PubMed] [Google Scholar]
  11. Jormalainen S., Mäkelä O. Anti-hapten antibodies in normal sera. Eur J Immunol. 1971 Dec;1(6):471–478. doi: 10.1002/eji.1830010613. [DOI] [PubMed] [Google Scholar]
  12. Leapman S. B., Filo R. S., Smith E. J., Smith P. G. In vitro effects of cyclosporin A on lymphocyte subpopulations. 1. Suppressor cell sparing by cyclosporin A. Transplantation. 1980 Dec;30(6):404–408. doi: 10.1097/00007890-198012000-00003. [DOI] [PubMed] [Google Scholar]
  13. Lowe J., Bird P., Hardie D., Jefferis R., Ling N. R. Monoclonal antibodies (McAbs) to determinants on human gamma chains: properties of antibodies showing subclass restriction or subclass specificity. Immunology. 1982 Oct;47(2):329–336. [PMC free article] [PubMed] [Google Scholar]
  14. Noel D. R., Witherspoon R. P., Storb R., Atkinson K., Doney K., Mickelson E. M., Ochs H. D., Warren R. P., Weiden P. L., Thomas E. D. Does graft-versus-host disease influence the tempo of immunologic recovery after allogeneic human marrow transplantation? An observation on 56 long-term survivors. Blood. 1978 Jun;51(6):1087–1105. [PubMed] [Google Scholar]
  15. Ochs H. D., Davis S. D., Wedgwood R. J. Immunologic responses to bacteriophage phi-X 174 in immunodeficiency diseases. J Clin Invest. 1971 Dec;50(12):2559–2568. doi: 10.1172/JCI106756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Rowley M. J., Mackay I. R. Measurement of antibody-producing capacity in man. I. The normal response to flagellin from Salmonella adelaide. Clin Exp Immunol. 1969 Oct;5(4):407–418. [PMC free article] [PubMed] [Google Scholar]
  17. Sarvas H. O., Aaltonen L. M., Péterfy F., Seppälä I. J., Mäkelä O. IgG subclass distributions in anti-hapten and anti-polysaccharide antibodies induced by haptenated polysaccharides. Eur J Immunol. 1983 May;13(5):409–414. doi: 10.1002/eji.1830130511. [DOI] [PubMed] [Google Scholar]
  18. Sharon R., McMaster P. R., Kask A. M., Owens J. D., Paul W. E. DNP-Lys-ficoll: a T-independent antigen which elicits both IgM and IgG anti-DNP antibody-secreting cells. J Immunol. 1975 May;114(5):1585–1589. [PubMed] [Google Scholar]
  19. Sokal J. E. Editorial: Measurement of delayed skin-test responses. N Engl J Med. 1975 Sep 4;293(10):501–502. doi: 10.1056/NEJM197509042931013. [DOI] [PubMed] [Google Scholar]
  20. Sweny P., Tidman N. The effect of cyclosporin A on peripheral blood T cell subpopulations in renal allografts. Clin Exp Immunol. 1982 Feb;47(2):445–448. [PMC free article] [PubMed] [Google Scholar]
  21. Trefts P. E., Rivier D. A., Kagnoff M. F. T cell-dependent IgA anti-polysaccharide response in vitro. Nature. 1981 Jul 9;292(5819):163–164. doi: 10.1038/292163a0. [DOI] [PubMed] [Google Scholar]
  22. Winston D. J., Schiffman G., Wang D. C., Feig S. A., Lin C. H., Marso E. L., Ho W. G., Young L. S., Gale R. P. Pneumococcal infections after human bone-marrow transplantation. Ann Intern Med. 1979 Dec;91(6):835–841. doi: 10.7326/0003-4819-91-6-835. [DOI] [PubMed] [Google Scholar]
  23. Yount W. J., Dorner M. M., Kunkel H. G., Kabat E. A. Studies on human antibodies. VI. Selective variations in subgroup composition and genetic markers. J Exp Med. 1968 Mar 1;127(3):633–646. doi: 10.1084/jem.127.3.633. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES