Skip to main content

Advertisement

Log in

Immunohistochemical study of γ δ T cell receptor-positive cells in the capsular region of hepatocellular carcinoma: Possible role in defense against expansion of carcinoma in the liver

  • Liver, Pancreas, and Biliary Tract
  • Published:
Journal of Gastroenterology Aims and scope Submit manuscript

Abstract

The localization and distribution of γ δ T cell receptor (TCR)-positive cells (γ δ T cells) in hepatocellular carcinoma capsules was investigated immuno-histochemically at both light and electron microscopic levels. Most of the mononuclear cells infiltrating the tumor capsules were CD3-positive. Together with γ δ T cells, they were significantly increased in the tumor capsules compared to amounts in the fibrous septa in non-cancerous cirrhotic areas of the same liver, and cirrhosis. Phenotypic characterization by the two-color double-staining technique showed that CD8γ δ cells were significantly increased in the tumor capsule, and that more than one-third of γ δ TCR-positive cells also expressed the CD56 antigen. Morphological observation revealed that large γ δ T cells were increased in number in the tumor capsule and that the cytoplasm of these cells contained multivesicular bodies and dense granules. These morphological features were similar to those of large granular lymphocytes, and most of the γ δ T cells were also positive for BB3. This suggests that extrathymic maturation of γ δ T cells occurs in the tumor capsule, and that these γ δ T cells may have a cytolytic effect on tumor cells, as shown in large gramular lymphocytes; further, the results suggest that these cells may play a role in the defense against tumor expansion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Bonneville M. Intestinal intraepithelial lymphocytes are a distinct set of γ δ T cells. Nature 1988;336:479–481.

    Article  CAS  PubMed  Google Scholar 

  2. Takagaki Y, Decloux A, Bonneville M, et al. Diversity of γ δ T cell receptors on murine intestinal intraepithelial lymphocytes. Nature 1989;339:712–714.

    Article  CAS  PubMed  Google Scholar 

  3. Koning F, Stingl, G, Yokoyama WM, et al. Identification of a T3-associated γ δ T cell receptor on Thy-1+ dendritic epidermal cell lines. Science 1987;236:834–837.

    CAS  PubMed  Google Scholar 

  4. Kuziel WA, Takashima A, Bonyhadi M, et al. Regulation of T-cell receptor δ-chain RNA expression in murine Thy-1+ dendritic epidermal cells. Nature 1987;328:263–266.

    Article  CAS  PubMed  Google Scholar 

  5. Havran WL, Grell S, Duwe G, et al. Limited diversity of T-cell receptor δ-chain expression of murine Thy-1+ dendritic epidermal cells revealed by V γ 3-specific monoclonal antibody. Proc Natl Acad Sci USA 1989;86:4185–4189.

    CAS  PubMed  Google Scholar 

  6. Augustin A, Kubo R, Sim GK. Resident pulmonary lymphocytes expressing the γ/δ T-cell receptor. Nature 1989;340:239–241.

    Article  CAS  PubMed  Google Scholar 

  7. Rajasekar R, Sim GK. Self heat shock and γ δ T-cell reactivity. Proc Natl Acad Sci USA 1990;87:1767–1771.

    CAS  PubMed  Google Scholar 

  8. Kabelitz D. Function and specificity of human γ/δ-positive T cells. Crit Rev Immunol 1992;11:281–303.

    CAS  PubMed  Google Scholar 

  9. Morita CT, Verma S. Functionally distinct subsets of human γ/δ T cells. Eur J Immunol 1991;21:2999–3007.

    CAS  PubMed  Google Scholar 

  10. Saito T, Pardoll DM. A murine thymocyte clone expressing γ δ T-cell receptor mediates natural killer-like cytolytic function and TH1-like lymphokine production. Cell Immunol 1990;131:284–301.

    Article  CAS  PubMed  Google Scholar 

  11. Soderatrom K, Halapi E. Synovial cells responding to a 65-kDa mycobacterial heat shock protein have a high proportion of a TcR γ δ subtype uncommon in peripheral blood. Scand J Immunol 1990;32:503–515.

    Google Scholar 

  12. Moretta L, Ciccone E. Human T lymphocytes expressing γ/δ T cell antigen receptor. Clin Immunol Immunopathol 1989;50:S117–123.

    Article  Google Scholar 

  13. Seki S, Nagura H. Identification of activated T cell receptor γ δ lymphocytes in the liver of tumor-bearing hosts. J Clin Invest 1990;86:409–415.

    CAS  PubMed  Google Scholar 

  14. Alam SM, Clark JS. T cell receptor gamma/delta expression on lymphocyte populations of breast cancer patients. Immunol Lett 1992;31:279–284.

    Article  CAS  PubMed  Google Scholar 

  15. Yoshino I. T lymphocytes bearing γ/δ-type T-cell receptor in thymic tumor tissues. J Natl Cancer Inst 1992;84:22, 1755.

    Google Scholar 

  16. Kanayama K, Morise K. Immunohistochemical study of T cell receptor γ δ cells in chronic liver disease. Am J Gastroenterol 1992;87:1018–1022.

    CAS  PubMed  Google Scholar 

  17. Grossi CE, Ciccone E, Migone N, et al. Human T cells expressing the γ δ T-cell receptor (TcR-1): C γ 1- and C γ 2-encoded forms of the receptor correlate with distinctive morphology, cytoskeletal organization, and growth characteristics. Proc Natl Acad Sci USA 1989;86:1619–1623.

    CAS  PubMed  Google Scholar 

  18. Fukushima K, Masuda T. Immunohistochemical characterization, distribution, and ultrastructure of lymphocytes bearing T-cell receptor γ/δ in inflammatory bowel disease. Gastroenterology 1991;101:670–678.

    CAS  PubMed  Google Scholar 

  19. Ohtani H, Nakamura, S, Nagura H, et al. Immunocytochemical localization of basic fibroblast growth factor in carcinomas and inflammatory lesions of the human digestive tract. Lab Invest 1993;68:520–527.

    CAS  PubMed  Google Scholar 

  20. Mizoi T, Ohtani H, Nagura H, et al. Immunoelectron microscopic localization of transforming growth factor β 1 binding protein in human gastrointestinal carcinomas: Qualitative difference between cancer cells and stromal cells. Cancer Res 1993;53:183–190.

    CAS  PubMed  Google Scholar 

  21. Goodman T, Lefrancoes L. Expression of the γ δ T-cell receptor on intestinal CD8+ intraepithelial lymphocytes. Nature 1988;333:855–858.

    Article  CAS  PubMed  Google Scholar 

  22. Bottino C, Tambussi G, Fertini S, et al. Two subsets of human T lymphocytes expressing γ/δ antigen receptor are identifiable by monoclonal antibodies directed to two distinct molecular forms of the receptor. J Exp Med 1988;168:491–505.

    Article  CAS  PubMed  Google Scholar 

  23. Ferrarini M. A lympholiferative disorder of the large granular lymphocytes with natural killer activity. J Clin Immunol 1983;3:30–41.

    Article  CAS  PubMed  Google Scholar 

  24. Barlozzari T, Leonhardt J. Direct evidence for the role of LGL in the inhibition of experimental tumor metastases. J Immunol 1985;134:2783–2789.

    CAS  PubMed  Google Scholar 

  25. Raulet DH. Antigents for γ/δ T cells. Nature 1989;339:342–343.

    Article  CAS  PubMed  Google Scholar 

  26. Young RA, Elliott TJ. Stress proteins, infection, and immune surveillance. Cell 1989;59:5–8.

    Article  CAS  PubMed  Google Scholar 

  27. Nicholas B, Thangue La, Latchman D. A cellular protein related to heat-shock protein 90 accumulates duringHerpes simplex virus infection and is overexpressed in transformed cells. Exp Cell Res 1988;178:169–179.

    Google Scholar 

  28. Wand-Wurttenberger A, Schoel B. Surface expression by mononuclear phagocytes of an epitope shared with mycobacterial heat shock protein 60. Eur J Immunol 1991;21:1089–1092.

    CAS  PubMed  Google Scholar 

  29. Koga T, Wand-Wurttenberger A. T cells against a bacterial heat shock protein recognize stressed macrophages. Science 1989;245:1112–1115.

    CAS  PubMed  Google Scholar 

  30. van Ravenswaay Claasen HH, Kluin PM. Tumor infiltrating cells in human cancer-on the possible role of CD16+ macrophages in antitumor cytotoxicity. Lab Invest 1992;57:166–174.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chin, K., Morise, K., Kanayama, K. et al. Immunohistochemical study of γ δ T cell receptor-positive cells in the capsular region of hepatocellular carcinoma: Possible role in defense against expansion of carcinoma in the liver. J Gastroenterol 30, 330–337 (1995). https://doi.org/10.1007/BF02347508

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02347508

Key words

Navigation