Skip to main content
PMC home page
British Journal of Cancer logoLink to British Journal of Cancer
. 2001 May;84(10):1339–1343. doi: 10.1054/bjoc.2001.1792

The effect of peripheral blood lymphocyte stimulation on zeta chain expression and IL-2 production in Hodgkin's disease

I Frydecka 1,2, D Boćko 2, A Kosmaczewska 2, L Ciszak 2, R Morilla 3
PMCID: PMC2363644  PMID: 11355944

Abstract

It has been reported that peripheral blood T cells and NK cells express reduced levels of the T-cell receptor signal-transducing zeta chain in Hodgkin's disease (HD). The zeta chain has emerged as a key subunit of the T-cell antigen receptor, which plays a central role in the signal-transducing events leading to T and NK-cell activation. We were interested in determining whether the low zeta chain expression in HD could be corrected by anti-CD3, anti-CD3-rIL-2 ex vivo stimulation. Zeta chain expression was analysed by dual immunofluorescence on permeabilized cells before and after 72 hours of culture. The IL-2 concentration in the culture supernatants was measured by ELISA. Zeta chain was significantly reduced on unstimulated CD4+, CD8+ and CD56+ cells from patients in active disease compared with normal subjects. In patients in complete remission, the values were normal except for CD8+ cells, on which zeta expression remained significantly reduced. Stimulation with anti-CD3 did not change zeta expression. Co-stimulation with rIL-2 increased but did not normalize the proportions of CD4+/zeta+, CD8+/zeta+and CD56+/zeta+cells and IL-2 production in active disease. Stimulation of cells from patients in clinical remission with anti-CD3+rIL-2 increased the proportion of CD8+zeta+cells and normalized IL-2 production levels. Considering the pivotal role of CD3-zeta in immune response, our data suggest that successful immunotherapy approaches in active HD should consider inclusion of other potent cytokines, as well as genetically engineered tumour vaccines. © 2001 Cancer Research Campaign www.bjcancer.com

Keywords: Hodgkin's disease, lymphocytes, zeta chain, stimulation

Full Text

The Full Text of this article is available as a PDF (59.4 KB).

Selected References

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

  1. Anderson P., Blue M. L., O'Brien C., Schlossman S. F. Monoclonal antibodies reactive with the T cell receptor zeta chain: production and characterization using a new method. J Immunol. 1989 Sep 15;143(6):1899–1904. [PubMed] [Google Scholar]
  2. Anderson P., Caligiuri M., O'Brien C., Manley T., Ritz J., Schlossman S. F. Fc gamma receptor type III (CD16) is included in the zeta NK receptor complex expressed by human natural killer cells. Proc Natl Acad Sci U S A. 1990 Mar;87(6):2274–2278. doi: 10.1073/pnas.87.6.2274. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Carbone P. P., Kaplan H. S., Musshoff K., Smithers D. W., Tubiana M. Report of the Committee on Hodgkin's Disease Staging Classification. Cancer Res. 1971 Nov;31(11):1860–1861. [PubMed] [Google Scholar]
  4. Farace F., Angevin E., Vanderplancke J., Escudier B., Triebel F. The decreased expression of CD3 zeta chains in cancer patients is not reversed by IL-2 administration. Int J Cancer. 1994 Dec 15;59(6):752–755. doi: 10.1002/ijc.2910590607. [DOI] [PubMed] [Google Scholar]
  5. Finke J. H., Zea A. H., Stanley J., Longo D. L., Mizoguchi H., Tubbs R. R., Wiltrout R. H., O'Shea J. J., Kudoh S., Klein E. Loss of T-cell receptor zeta chain and p56lck in T-cells infiltrating human renal cell carcinoma. Cancer Res. 1993 Dec 1;53(23):5613–5616. [PubMed] [Google Scholar]
  6. Frydecka I., Kaczmarek P., Boćko D., Kosmaczewska A., Ciszak L. Alterations in signal transducing molecule CD3 zeta in patients with neoplastic diseases. Arch Immunol Ther Exp (Warsz) 1998;46(6):355–359. [PubMed] [Google Scholar]
  7. Frydecka I., Kaczmarek P., Boćko D., Kosmaczewska A., Morilla R., Catovsky D. Expression of signal-transducing zeta chain in peripheral blood T cells and natural killer cells in patients with Hodgkin's disease in different phases of the disease. Leuk Lymphoma. 1999 Nov;35(5-6):545–554. doi: 10.1080/10428199909169619. [DOI] [PubMed] [Google Scholar]
  8. Guarini A., Riera L., Cignetti A., Montacchini L., Massaia M., Foa R. Transfer of the interleukin-2 gene into human cancer cells induces specific antitumor recognition and restores the expression of CD3/T-cell receptor associated signal transduction molecules. Blood. 1997 Jan 1;89(1):212–218. [PubMed] [Google Scholar]
  9. Irving B. A., Weiss A. The cytoplasmic domain of the T cell receptor zeta chain is sufficient to couple to receptor-associated signal transduction pathways. Cell. 1991 Mar 8;64(5):891–901. doi: 10.1016/0092-8674(91)90314-o. [DOI] [PubMed] [Google Scholar]
  10. Kiessling R., Wasserman K., Horiguchi S., Kono K., Sjöberg J., Pisa P., Petersson M. Tumor-induced immune dysfunction. Cancer Immunol Immunother. 1999 Oct;48(7):353–362. doi: 10.1007/s002620050586. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Matsuda M., Petersson M., Lenkei R., Taupin J. L., Magnusson I., Mellstedt H., Anderson P., Kiessling R. Alterations in the signal-transducing molecules of T cells and NK cells in colorectal tumor-infiltrating, gut mucosal and peripheral lymphocytes: correlation with the stage of the disease. Int J Cancer. 1995 Jun 9;61(6):765–772. doi: 10.1002/ijc.2910610605. [DOI] [PubMed] [Google Scholar]
  12. Musci M. A., Latinis K. M., Koretzky G. A. Signaling events in T lymphocytes leading to cellular activation or programmed cell death. Clin Immunol Immunopathol. 1997 Jun;83(3):205–222. doi: 10.1006/clin.1996.4315. [DOI] [PubMed] [Google Scholar]
  13. Nakagomi H., Petersson M., Magnusson I., Juhlin C., Matsuda M., Mellstedt H., Taupin J. L., Vivier E., Anderson P., Kiessling R. Decreased expression of the signal-transducing zeta chains in tumor-infiltrating T-cells and NK cells of patients with colorectal carcinoma. Cancer Res. 1993 Dec 1;53(23):5610–5612. [PubMed] [Google Scholar]
  14. Rabinowich H., Banks M., Reichert T. E., Logan T. F., Kirkwood J. M., Whiteside T. L. Expression and activity of signaling molecules in T lymphocytes obtained from patients with metastatic melanoma before and after interleukin 2 therapy. Clin Cancer Res. 1996 Aug;2(8):1263–1274. [PubMed] [Google Scholar]
  15. Tartour E., Latour S., Mathiot C., Thiounn N., Mosseri V., Joyeux I., D'Enghien C. D., Lee R., Debre B., Fridman W. H. Variable expression of CD3-zeta chain in tumor-infiltrating lymphocytes (TIL) derived from renal-cell carcinoma: relationship with TIL phenotype and function. Int J Cancer. 1995 Oct 9;63(2):205–212. doi: 10.1002/ijc.2910630210. [DOI] [PubMed] [Google Scholar]
  16. Vivier E., Morin P., O'Brien C., Druker B., Schlossman S. F., Anderson P. Tyrosine phosphorylation of the Fc gamma RIII(CD16): zeta complex in human natural killer cells. Induction by antibody-dependent cytotoxicity but not by natural killing. J Immunol. 1991 Jan 1;146(1):206–210. [PubMed] [Google Scholar]
  17. Weissman A. M., Baniyash M., Hou D., Samelson L. E., Burgess W. H., Klausner R. D. Molecular cloning of the zeta chain of the T cell antigen receptor. Science. 1988 Feb 26;239(4843):1018–1021. doi: 10.1126/science.3278377. [DOI] [PubMed] [Google Scholar]
  18. Whiteside T. L. Signaling defects in T lymphocytes of patients with malignancy. Cancer Immunol Immunother. 1999 Oct;48(7):346–352. doi: 10.1007/s002620050585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Yoong K. F., Adams D. H. Interleukin 2 restores CD3-zeta chain expression but fails to generate tumour-specific lytic activity in tumour-infiltrating lymphocytes derived from human colorectal hepatic metastases. Br J Cancer. 1998 Apr;77(7):1072–1081. doi: 10.1038/bjc.1998.179. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Zea A. H., Curti B. D., Longo D. L., Alvord W. G., Strobl S. L., Mizoguchi H., Creekmore S. P., O'Shea J. J., Powers G. C., Urba W. J. Alterations in T cell receptor and signal transduction molecules in melanoma patients. Clin Cancer Res. 1995 Nov;1(11):1327–1335. [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES