Skip to main content
PMC home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1992 Mar;87(3):493–498. doi: 10.1111/j.1365-2249.1992.tb03025.x

IL-2 infusion abrogates humoral immune responses in humans.

D J Gottlieb 1, H G Prentice 1, H E Heslop 1, C Bello 1, M K Brenner 1
PMCID: PMC1554326  PMID: 1544235

Abstract

Although IL-2 infusion enhances cell-mediated cytotoxicity in patients with neoplastic disease, administration is paradoxically associated with a modest fall in total serum IgG and an increased risk of infection. We now show that the adverse effects of IL-2 infusion on the humoral immune system are substantial. Although IL-2 induces the B cell growth and differentiating factors IL-4 and IL-6, infusion abrogates primary antibody responses entirely and reduces secondary antibody responses 50-fold following antigen challenge. There is no evidence of the generation of cells with suppressive activity on B cells but IL-2 increases the ratio of circulating virgin:memory cells. These results may help to explain the increased rate of bacterial infection in patients receiving IL-2. As IL-2 plays a central role in the generation of an immune response, the finding that it is also sufficiently immunosuppressive to inhibit primary- and secondary-type antibody responses suggests that exploration of the underlying mechanisms may provide insights into immune system homeostasis and may offer new approaches to therapeutic immunosuppression.

Full text

PDF
493

Images in this article

495Fig. 1
on p.495

Selected References

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

  1. Aarden L. A., De Groot E. R., Schaap O. L., Lansdorp P. M. Production of hybridoma growth factor by human monocytes. Eur J Immunol. 1987 Oct;17(10):1411–1416. doi: 10.1002/eji.1830171004. [DOI] [PubMed] [Google Scholar]
  2. Akbar A. N., Amlot P. L., Timms A., Lombardi G., Lechler R., Janossy G. The development of primed/memory CD8+ lymphocytes in vitro and in rejecting kidneys after transplantation. Clin Exp Immunol. 1990 Aug;81(2):225–231. doi: 10.1111/j.1365-2249.1990.tb03322.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Amlot P. L., Hayes A. E., Gray D., Gordon-Smith E. C., Humphrey J. H. Human immune responses in vivo to protein (KLH) and polysaccharide (DNP-Ficoll) neoantigens: normal subjects compared with bone marrow transplant patients on cyclosporine. Clin Exp Immunol. 1986 Apr;64(1):125–135. [PMC free article] [PubMed] [Google Scholar]
  4. Bock S. N., Lee R. E., Fisher B., Rubin J. T., Schwartzentruber D. J., Wei J. P., Callender D. P., Yang J. C., Lotze M. T., Pizzo P. A. A prospective randomized trial evaluating prophylactic antibiotics to prevent triple-lumen catheter-related sepsis in patients treated with immunotherapy. J Clin Oncol. 1990 Jan;8(1):161–169. doi: 10.1200/JCO.1990.8.1.161. [DOI] [PubMed] [Google Scholar]
  5. Brod S. A., Rudd C. E., Purvee M., Hafler D. A. Lymphokine regulation of CD45R expression on human T cell clones. J Exp Med. 1989 Dec 1;170(6):2147–2152. doi: 10.1084/jem.170.6.2147. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Callard R. E., Smith S. H., Shields J. G., Levinsky R. J. T cell help in human antigen-specific antibody responses can be replaced by interleukin 2. Eur J Immunol. 1986 Sep;16(9):1037–1042. doi: 10.1002/eji.1830160902. [DOI] [PubMed] [Google Scholar]
  7. Campana D., Janossy G. Leukemia diagnosis and testing of complement-fixing antibodies for bone marrow purging in acute lymphoid leukemia. Blood. 1986 Dec;68(6):1264–1271. [PubMed] [Google Scholar]
  8. Gottlieb D. J., Brenner M. K., Heslop H. E., Bianchi A. C., Bello-Fernandez C., Mehta A. B., Newland A. C., Galazka A. R., Scott E. M., Hoffbrand A. V. A phase I clinical trial of recombinant interleukin 2 following high dose chemo-radiotherapy for haematological malignancy: applicability to the elimination of minimal residual disease. Br J Cancer. 1989 Oct;60(4):610–615. doi: 10.1038/bjc.1989.324. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gottlieb D. J., Prentice H. G., Heslop H. E., Bello-Fernandez C., Bianchi A. C., Galazka A. R., Brenner M. K. Effects of recombinant interleukin-2 administration on cytotoxic function following high-dose chemo-radiotherapy for hematological malignancy. Blood. 1989 Nov 15;74(7):2335–2342. [PubMed] [Google Scholar]
  10. Heslop H. E., Gottlieb D. J., Bianchi A. C., Meager A., Prentice H. G., Mehta A. B., Hoffbrand A. V., Brenner M. K. In vivo induction of gamma interferon and tumor necrosis factor by interleukin-2 infusion following intensive chemotherapy or autologous marrow transplantation. Blood. 1989 Sep;74(4):1374–1380. [PubMed] [Google Scholar]
  11. Howard M., Matis L., Malek T. R., Shevach E., Kell W., Cohen D., Nakanishi K., Paul W. E. Interleukin 2 induces antigen-reactive T cell lines to secrete BCGF-I. J Exp Med. 1983 Dec 1;158(6):2024–2039. doi: 10.1084/jem.158.6.2024. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jelinek D. F., Lipsky P. E. Enhancement of human B cell proliferation and differentiation by tumor necrosis factor-alpha and interleukin 1. J Immunol. 1987 Nov 1;139(9):2970–2976. [PubMed] [Google Scholar]
  13. Llorente L., Crevon M. C., Karray S., Defrance T., Banchereau J., Galanaud P. Interleukin (IL) 4 counteracts the helper effect of IL2 on antigen-activated human B cells. Eur J Immunol. 1989 Apr;19(4):765–769. doi: 10.1002/eji.1830190429. [DOI] [PubMed] [Google Scholar]
  14. Meuer S. C., Dumann H., Meyer zum Büschenfelde K. H., Köhler H. Low-dose interleukin-2 induces systemic immune responses against HBsAg in immunodeficient non-responders to hepatitis B vaccination. Lancet. 1989 Jan 7;1(8628):15–18. doi: 10.1016/s0140-6736(89)91674-7. [DOI] [PubMed] [Google Scholar]
  15. Oshimi K., Oshimi Y., Saito H., Mizoguchi H. Cytotoxicity of interleukin-2-activated lymphocytes for autologous normal blood mononuclear cells. J Immunol Methods. 1988 May 9;109(2):161–168. doi: 10.1016/0022-1759(88)90238-4. [DOI] [PubMed] [Google Scholar]
  16. Ralph P., Jeong G., Welte K., Mertelsmann R., Rabin H., Henderson L. E., Souza L. M., Boone T. C., Robb R. J. Stimulation of immunoglobulin secretion in human B lymphocytes as a direct effect of high concentrations of IL 2. J Immunol. 1984 Nov;133(5):2442–2445. [PubMed] [Google Scholar]
  17. Romagnani S., Giudizi M. G., Biagiotti R., Almerigogna F., Mingari C., Maggi E., Liang C. M., Moretta L. B cell growth factor activity of interferon-gamma. Recombinant human interferon-gamma promotes proliferation of anti-mu-activated human B lymphocytes. J Immunol. 1986 May 15;136(10):3513–3516. [PubMed] [Google Scholar]
  18. Rosenberg S. A., Lotze M. T., Muul L. M., Chang A. E., Avis F. P., Leitman S., Linehan W. M., Robertson C. N., Lee R. E., Rubin J. T. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med. 1987 Apr 9;316(15):889–897. doi: 10.1056/NEJM198704093161501. [DOI] [PubMed] [Google Scholar]
  19. Smith S. H., Brown M. H., Rowe D., Callard R. E., Beverley P. C. Functional subsets of human helper-inducer cells defined by a new monoclonal antibody, UCHL1. Immunology. 1986 May;58(1):63–70. [PMC free article] [PubMed] [Google Scholar]
  20. Suzuki H., Yamashita N., Maruyama M., Yoshikawa T., Yano S. Human lymphokine-activated killer cells suppress pokeweed mitogen-induced immunoglobulin synthesis. Clin Exp Immunol. 1989 Dec;78(3):406–411. [PMC free article] [PubMed] [Google Scholar]
  21. Waldmann T. A., Goldman C. K., Robb R. J., Depper J. M., Leonard W. J., Sharrow S. O., Bongiovanni K. F., Korsmeyer S. J., Greene W. C. Expression of interleukin 2 receptors on activated human B cells. J Exp Med. 1984 Nov 1;160(5):1450–1466. doi: 10.1084/jem.160.5.1450. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Wiebke E. A., Rosenberg S. A., Lotze M. T. Acute immunologic effects of interleukin-2 therapy in cancer patients: decreased delayed type hypersensitivity response and decreased proliferative response to soluble antigens. J Clin Oncol. 1988 Sep;6(9):1440–1449. doi: 10.1200/JCO.1988.6.9.1440. [DOI] [PubMed] [Google Scholar]
  23. Wimperis J. Z., Brenner M. K., Prentice H. G., Reittie J. E., Karayiannis P., Griffiths P. D., Hoffbrand A. V. Transfer of a functioning humoral immune system in transplantation of T-lymphocyte-depleted bone marrow. Lancet. 1986 Feb 15;1(8477):339–343. doi: 10.1016/s0140-6736(86)92315-9. [DOI] [PubMed] [Google Scholar]
  24. Wimperis J. Z., Gottlieb D., Duncombe A. S., Heslop H. E., Prentice H. G., Brenner M. K. Requirements for the adoptive transfer of antibody responses to a priming antigen in man. J Immunol. 1990 Jan 15;144(2):541–547. [PubMed] [Google Scholar]

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

RESOURCES