Skip to main content
NCBI home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1995 May 1;181(5):1881–1886. doi: 10.1084/jem.181.5.1881

Activated macrophages induce structural abnormalities of the T cell receptor-CD3 complex

PMCID: PMC2192011  PMID: 7722462

Abstract

The mechanism of the structural alterations of the T cell receptor (TCR)-CD3 complex, which appear to be greatly responsible for immunosuppression in the tumor-bearing status, was investigated in tumor-bearing mice. Splenic T cells from tumor-bearing hosts lost the expression of the CD3 zeta chain without being replaced by FcR gamma, despite the normal expression of other components of the TCR complex. Tumor growth induced the accumulation of non-T, non-B cells in the spleen in correlation with the loss of zeta. Those cells were found to be macrophages that were able to induce the loss of zeta, as well as structural changes of CD3 gamma delta epsilon, even in freshly isolated normal T cells by cell contact-dependent interaction. More importantly, macrophages activated with zymosan A+LPS but not residential macrophages were able to induce the similar abnormality of the TCR complex. These results indicate that macrophages in certain activation stages play a crucial role in causing an abnormal TCR complex in tumor- bearing conditions, as well as in regulating the structure of the TCR complex in immune responses.

Full Text

The Full Text of this article is available as a PDF (1.1 MB).

Selected References

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

  1. Alleva D. G., Burger C. J., Elgert K. D. Interferon-gamma reduces tumor-induced Ia- macrophage-mediated suppression: role of prostaglandin E2, Ia, and tumor necrosis factor-alpha. Immunopharmacology. 1993 May-Jun;25(3):215–227. doi: 10.1016/0162-3109(93)90050-z. [DOI] [PubMed] [Google Scholar]
  2. Bikoff E. K., Huang L. Y., Episkopou V., van Meerwijk J., Germain R. N., Robertson E. J. Defective major histocompatibility complex class II assembly, transport, peptide acquisition, and CD4+ T cell selection in mice lacking invariant chain expression. J Exp Med. 1993 Jun 1;177(6):1699–1712. doi: 10.1084/jem.177.6.1699. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. 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]
  4. Fujimoto S., Greene M. I., Sehon A. H. Regulation of the immune response to tumor antigens. II. The nature of immunosuppressor cells in tumor-bearing hosts. J Immunol. 1976 Mar;116(3):800–806. [PubMed] [Google Scholar]
  5. Gunji Y., Hori S., Aoe T., Asano T., Ochiai T., Isono K., Saito T. High frequency of cancer patients with abnormal assembly of the T cell receptor-CD3 complex in peripheral blood T lymphocytes. Jpn J Cancer Res. 1994 Dec;85(12):1189–1192. doi: 10.1111/j.1349-7006.1994.tb02927.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Ishikawa H., Li Y., Abeliovich A., Yamamoto S., Kaufmann S. H., Tonegawa S. Cytotoxic and interferon gamma-producing activities of gamma delta T cells in the mouse intestinal epithelium are strain dependent. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8204–8208. doi: 10.1073/pnas.90.17.8204. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Malissen B., Schmitt-Verhulst A. M. Transmembrane signalling through the T-cell-receptor-CD3 complex. Curr Opin Immunol. 1993 Jun;5(3):324–333. doi: 10.1016/0952-7915(93)90049-x. [DOI] [PubMed] [Google Scholar]
  9. Mantovani A., Bottazzi B., Colotta F., Sozzani S., Ruco L. The origin and function of tumor-associated macrophages. Immunol Today. 1992 Jul;13(7):265–270. doi: 10.1016/0167-5699(92)90008-U. [DOI] [PubMed] [Google Scholar]
  10. Miyake K., Weissman I. L., Greenberger J. S., Kincade P. W. Evidence for a role of the integrin VLA-4 in lympho-hemopoiesis. J Exp Med. 1991 Mar 1;173(3):599–607. doi: 10.1084/jem.173.3.599. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mizoguchi H., O'Shea J. J., Longo D. L., Loeffler C. M., McVicar D. W., Ochoa A. C. Alterations in signal transduction molecules in T lymphocytes from tumor-bearing mice. Science. 1992 Dec 11;258(5089):1795–1798. doi: 10.1126/science.1465616. [DOI] [PubMed] [Google Scholar]
  12. 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]
  13. Nelson J. A., Parhar R. S., Scodras J. M., Lala P. K. Down-regulation of macrophage I-A expression in tumor-bearing mice. J Leukoc Biol. 1990 Nov;48(5):394–402. doi: 10.1002/jlb.48.5.394. [DOI] [PubMed] [Google Scholar]
  14. Ohno H., Aoe T., Taki S., Kitamura D., Ishida Y., Rajewsky K., Saito T. Developmental and functional impairment of T cells in mice lacking CD3 zeta chains. EMBO J. 1993 Nov;12(11):4357–4366. doi: 10.1002/j.1460-2075.1993.tb06120.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ohno H., Ono S., Hirayama N., Shimada S., Saito T. Preferential usage of the Fc receptor gamma chain in the T cell antigen receptor complex by gamma/delta T cells localized in epithelia. J Exp Med. 1994 Jan 1;179(1):365–369. doi: 10.1084/jem.179.1.365. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Sakata T., Iwagami S., Tsuruta Y., Suzuki S., Suzuki R. Study of natural lipocortin I. A potent mediator for macrophage-mediated immunosuppression in tumor-bearing mice. J Immunol. 1993 Nov 1;151(9):4964–4972. [PubMed] [Google Scholar]
  17. Sussman J. J., Bonifacino J. S., Lippincott-Schwartz J., Weissman A. M., Saito T., Klausner R. D., Ashwell J. D. Failure to synthesize the T cell CD3-zeta chain: structure and function of a partial T cell receptor complex. Cell. 1988 Jan 15;52(1):85–95. doi: 10.1016/0092-8674(88)90533-8. [DOI] [PubMed] [Google Scholar]
  18. Suttles J., Miller R. W., Tao X., Stout R. D. T cells which do not express membrane tumor necrosis factor-alpha activate macrophage effector function by cell contact-dependent signaling of macrophage tumor necrosis factor-alpha production. Eur J Immunol. 1994 Aug;24(8):1736–1742. doi: 10.1002/eji.1830240803. [DOI] [PubMed] [Google Scholar]
  19. Tada T., Ohzeki S., Utsumi K., Takiuchi H., Muramatsu M., Li X. F., Shimizu J., Fujiwara H., Hamaoka T. Transforming growth factor-beta-induced inhibition of T cell function. Susceptibility difference in T cells of various phenotypes and functions and its relevance to immunosuppression in the tumor-bearing state. J Immunol. 1991 Feb 1;146(3):1077–1082. [PubMed] [Google Scholar]

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

RESOURCES