Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1995 Oct;102(1):159–166. doi: 10.1111/j.1365-2249.1995.tb06650.x

Origin of CD57+ T cells which increase at tumour sites in patients with colorectal cancer.

T Okada 1, T Iiai 1, Y Kawachi 1, T Moroda 1, Y Takii 1, K Hatakeyama 1, T Abo 1
PMCID: PMC1553343  PMID: 7554383

Abstract

Human T cells carrying natural killer (NK) markers, CD57 or CD56 antigens, appear to be distinguishable from other T cell subsets in terms of their granular lymphocyte morphology and their numerical increase in patients with AIDS and in recipients of bone marrow transplantation. At the beginning of this study, we observed that CD57+ T cells as well as CD56+ T cells were abundant at tumour sites in many patients with colorectal cancer. Since all these findings for CD57+ T cells are quite similar to those of extrathymic T cells seen in mice, we investigated how CD57+ T cells are distributed to various immune organs in humans. They were found to be present mainly in the bone marrow and liver, but to be completely absent in the thymus. Similar to the case of extrathymic T cells in mice, they were observed to consist of double-negative CD4-8- subsets as well as single-positive subsets (preponderance of CD8+ cells), and to contain a considerable proportion of gamma delta T cells. These features are striking when compared with those of CD57- T cells, which are characterized by an abundance of CD4+ subsets and alpha beta T cells. Not only at tumour sites but also in the peripheral blood, some patients with colorectal cancer displayed elevated levels of CD57+ cells. These results suggest that CD57+ T cells may be of extrathymic origin, possibly originating in the bone marrow and liver, and may be associated with tumour immunity, similar to another extrathymic population of CD56+ T cells in humans.

Full text

PDF
159

Selected References

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

  1. Abo T., Balch C. M. A differentiation antigen of human NK and K cells identified by a monoclonal antibody (HNK-1). J Immunol. 1981 Sep;127(3):1024–1029. [PubMed] [Google Scholar]
  2. Abo T., Cooper M. D., Balch C. M. Characterization of HNK-1+ (Leu-7) human lymphocytes. I. Two distinct phenotypes of human NK cells with different cytotoxic capability. J Immunol. 1982 Oct;129(4):1752–1757. [PubMed] [Google Scholar]
  3. Abo T., Ohteki T., Seki S., Koyamada N., Yoshikai Y., Masuda T., Rikiishi H., Kumagai K. The appearance of T cells bearing self-reactive T cell receptor in the livers of mice injected with bacteria. J Exp Med. 1991 Aug 1;174(2):417–424. doi: 10.1084/jem.174.2.417. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Andreu-Sánchez J. L., Moreno de Alborán I. M., Marcos M. A., Sánchez-Movilla A., Martínez-A C., Kroemer G. Interleukin 2 abrogates the nonresponsive state of T cells expressing a forbidden T cell receptor repertoire and induces autoimmune disease in neonatally thymectomized mice. J Exp Med. 1991 Jun 1;173(6):1323–1329. doi: 10.1084/jem.173.6.1323. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Arinaga S., Karimine N., Nanbara S., Inoue H., Nakashima H., Ueo H., Akiyoshi T. Lymphokine-activated killer cell function of lymphocytes from regional lymph nodes in patients with gastric carcinoma. J Surg Oncol. 1995 Jan;58(1):44–49. doi: 10.1002/jso.2930580110. [DOI] [PubMed] [Google Scholar]
  6. Autran B., Leblond V., Sadat-Sowti B., Lefranc E., Got P., Sutton L., Binet J. L., Debre P. A soluble factor released by CD8+CD57+ lymphocytes from bone marrow transplanted patients inhibits cell-mediated cytolysis. Blood. 1991 May 15;77(10):2237–2241. [PubMed] [Google Scholar]
  7. Bandeira A., Itohara S., Bonneville M., Burlen-Defranoux O., Mota-Santos T., Coutinho A., Tonegawa S. Extrathymic origin of intestinal intraepithelial lymphocytes bearing T-cell antigen receptor gamma delta. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):43–47. doi: 10.1073/pnas.88.1.43. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dupuy d'Angeac A., Monier S., Jorgensen C., Gao Q., Travaglio-Encinoza A., Bologna C., Combe B., Sany J., Rème T. Increased percentage of CD3+, CD57+ lymphocytes in patients with rheumatoid arthritis. Correlation with duration of disease. Arthritis Rheum. 1993 May;36(5):608–612. doi: 10.1002/art.1780360506. [DOI] [PubMed] [Google Scholar]
  9. Elbe A., Kilgus O., Strohal R., Payer E., Schreiber S., Stingl G. Fetal skin: a site of dendritic epidermal T cell development. J Immunol. 1992 Sep 1;149(5):1694–1701. [PubMed] [Google Scholar]
  10. Gorochov G., Debré P., Leblond V., Sadat-Sowti B., Sigaux F., Autran B. Oligoclonal expansion of CD8+ CD57+ T cells with restricted T-cell receptor beta chain variability after bone marrow transplantation. Blood. 1994 Jan 15;83(2):587–595. [PubMed] [Google Scholar]
  11. Guy-Grand D., Cerf-Bensussan N., Malissen B., Malassis-Seris M., Briottet C., Vassalli P. Two gut intraepithelial CD8+ lymphocyte populations with different T cell receptors: a role for the gut epithelium in T cell differentiation. J Exp Med. 1991 Feb 1;173(2):471–481. doi: 10.1084/jem.173.2.471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hayakawa J., Shiohara T., Moriya N., Arahari K., Nagashima M., Yagita H., Ishikawa H. Identification of a novel population of CD8 alpha+ beta- bone marrow-derived dendritic epidermal cells. This unique population is subsequently outnumbered by thymus-independent expansion of the CD8 alpha+ beta+ dendritic epidermal cells. J Immunol. 1993 Dec 1;151(11):5984–5992. [PubMed] [Google Scholar]
  13. Hercend T., Griffin J. D., Bensussan A., Schmidt R. E., Edson M. A., Brennan A., Murray C., Daley J. F., Schlossman S. F., Ritz J. Generation of monoclonal antibodies to a human natural killer clone. Characterization of two natural killer-associated antigens, NKH1A and NKH2, expressed on subsets of large granular lymphocytes. J Clin Invest. 1985 Mar;75(3):932–943. doi: 10.1172/JCI111794. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Hilbe W., Eisterer W., Schmid C., Starz I., Silly H., Duba C., Ludescher C., Thaler J. Bone marrow lymphocyte subsets in myelodysplastic syndromes. J Clin Pathol. 1994 Jun;47(6):505–507. doi: 10.1136/jcp.47.6.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hirahara H., Ogawa M., Kimura M., Iiai T., Tsuchida M., Hanawa H., Watanabe H., Abo T. Glucocorticoid independence of acute thymic involution induced by lymphotoxin and estrogen. Cell Immunol. 1994 Feb;153(2):401–411. doi: 10.1006/cimm.1994.1038. [DOI] [PubMed] [Google Scholar]
  16. Iiai T., Watanabe H., Seki S., Sugiura K., Hirokawa K., Utsuyama M., Takahashi-Iwanaga H., Iwanaga T., Ohteki T., Abo T. Ontogeny and development of extrathymic T cells in mouse liver. Immunology. 1992 Dec;77(4):556–563. [PMC free article] [PubMed] [Google Scholar]
  17. Ikarashi Y., Abo T., Kawai K., IIai T., Watanabe H., Suzuki K., Matsumoto Y., Omata S., Fujiwara M. Expansion of intermediate T-cell receptor cells in mice with autoimmune-like graft-versus-host disease. Immunology. 1994 Oct;83(2):205–212. [PMC free article] [PubMed] [Google Scholar]
  18. Ishikawa H., Saito K. Congenitally athymic nude (nu/nu) mice have Thy-1-bearing immunocompetent helper T cells in their peritoneal cavity. J Exp Med. 1980 Apr 1;151(4):965–968. doi: 10.1084/jem.151.4.965. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Iwatani Y., Hidaka Y., Matsuzuka F., Kuma K., Amino N. Intrathyroidal lymphocyte subsets, including unusual CD4+ CD8+ cells and CD3loTCR alpha beta lo/-CD4-CD8- cells, in autoimmune thyroid disease. Clin Exp Immunol. 1993 Sep;93(3):430–436. doi: 10.1111/j.1365-2249.1993.tb08196.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Izquierdo M., Balboa M. A., Fernández-Rañada J. M., Figuera A., Torres A., Iriondo A., López-Botet M. Relation between the increase of circulating CD3+ CD57+ lymphocytes and T cell dysfunction in recipients of bone marrow transplantation. Clin Exp Immunol. 1990 Oct;82(1):145–150. doi: 10.1111/j.1365-2249.1990.tb05418.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Karimine N., Nanbara S., Arinaga S., Asoh T., Ueo H., Akiyoshi T. Lymphokine-activated killer cell activity of peripheral blood, spleen, regional lymph node, and tumor infiltrating lymphocytes in gastric cancer patients. J Surg Oncol. 1994 Mar;55(3):179–185. doi: 10.1002/jso.2930550310. [DOI] [PubMed] [Google Scholar]
  22. Kimura M., Watanabe H., Ohtsuka K., Iiai T., Tsuchida M., Sato S., Abo T. Radioresistance of intermediate TCR cells and their localization in the body of mice revealed by irradiation. Microbiol Immunol. 1993;37(8):641–652. doi: 10.1111/j.1348-0421.1993.tb01687.x. [DOI] [PubMed] [Google Scholar]
  23. Koyama S., Ebihara T., Fukao K. Expression of intercellular adhesion molecule 1 (ICAM-1) during the development of invasion and/or metastasis of gastric carcinoma. J Cancer Res Clin Oncol. 1992;118(8):609–614. doi: 10.1007/BF01211806. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kruse J., Mailhammer R., Wernecke H., Faissner A., Sommer I., Goridis C., Schachner M. Neural cell adhesion molecules and myelin-associated glycoprotein share a common carbohydrate moiety recognized by monoclonal antibodies L2 and HNK-1. Nature. 1984 Sep 13;311(5982):153–155. doi: 10.1038/311153a0. [DOI] [PubMed] [Google Scholar]
  25. Kubota H., Sato M., Ogawa Y., Iwai K., Hattori M., Yoshida T., Minato N. Involvement of 4F2 antigen expressed on the MHC-negative target cells in the recognition of murine CD3+CD4-CD8- alpha beta (V alpha 4/V beta 2) T cells. Int Immunol. 1994 Sep;6(9):1323–1331. doi: 10.1093/intimm/6.9.1323. [DOI] [PubMed] [Google Scholar]
  26. Kusunoki Y., Hirai Y., Hayashi T., Kyoizumi S., Takahashi K., Morishita Y., Kodama Y., Akiyama M. Frequent occurrence of in vivo clonal expansion of CD4- CD8- T cells bearing T cell receptor alpha beta chains in adult humans. Eur J Immunol. 1993 Nov;23(11):2735–2739. doi: 10.1002/eji.1830231102. [DOI] [PubMed] [Google Scholar]
  27. Kusunoki Y., Hirai Y., Kyoizumi S., Akiyama M. Evidence for in vivo clonal proliferation of unique population of blood CD4-/CD8- T cells bearing T-cell receptor alpha and beta chains in two normal men. Blood. 1992 Jun 1;79(11):2965–2972. [PubMed] [Google Scholar]
  28. Lanier L. L., Le A. M., Civin C. I., Loken M. R., Phillips J. H. The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol. 1986 Jun 15;136(12):4480–4486. [PubMed] [Google Scholar]
  29. Lanier L. L., Testi R., Bindl J., Phillips J. H. Identity of Leu-19 (CD56) leukocyte differentiation antigen and neural cell adhesion molecule. J Exp Med. 1989 Jun 1;169(6):2233–2238. doi: 10.1084/jem.169.6.2233. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Legac E., Autran B., Merle-Beral H., Katlama C., Debre P. CD4+CD7-CD57+ T cells: a new T-lymphocyte subset expanded during human immunodeficiency virus infection. Blood. 1992 Apr 1;79(7):1746–1753. [PubMed] [Google Scholar]
  31. Makino Y., Yamagata N., Sasho T., Adachi Y., Kanno R., Koseki H., Kanno M., Taniguchi M. Extrathymic development of V alpha 14-positive T cells. J Exp Med. 1993 May 1;177(5):1399–1408. doi: 10.1084/jem.177.5.1399. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ohteki T., Seki S., Abo T., Kumagai K. Liver is a possible site for the proliferation of abnormal CD3+4-8- double-negative lymphocytes in autoimmune MRL-lpr/lpr mice. J Exp Med. 1990 Jul 1;172(1):7–12. doi: 10.1084/jem.172.1.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ohtsuka K., Iiai T., Watanabe H., Tanaka T., Miyasaka M., Sato K., Asakura H., Abo T. Similarities and differences between extrathymic T cells residing in mouse liver and intestine. Cell Immunol. 1994 Jan;153(1):52–66. doi: 10.1006/cimm.1994.1005. [DOI] [PubMed] [Google Scholar]
  34. Sadat-Sowti B., Debré P., Mollet L., Quint L., Hadida F., Leblond V., Bismuth G., Autran B. An inhibitor of cytotoxic functions produced by CD8+CD57+ T lymphocytes from patients suffering from AIDS and immunosuppressed bone marrow recipients. Eur J Immunol. 1994 Nov;24(11):2882–2888. doi: 10.1002/eji.1830241145. [DOI] [PubMed] [Google Scholar]
  35. Schmidt R. E., Murray C., Daley J. F., Schlossman S. F., Ritz J. A subset of natural killer cells in peripheral blood displays a mature T cell phenotype. J Exp Med. 1986 Jul 1;164(1):351–356. doi: 10.1084/jem.164.1.351. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Seki S., Abo T., Ohteki T., Sugiura K., Kumagai K. Unusual alpha beta-T cells expanded in autoimmune lpr mice are probably a counterpart of normal T cells in the liver. J Immunol. 1991 Aug 15;147(4):1214–1221. [PubMed] [Google Scholar]
  37. Takii Y., Hashimoto S., Iiai T., Watanabe H., Hatakeyama K., Abo T. Increase in the proportion of granulated CD56+ T cells in patients with malignancy. Clin Exp Immunol. 1994 Sep;97(3):522–527. doi: 10.1111/j.1365-2249.1994.tb06120.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Wang E. C., Taylor-Wiedeman J., Perera P., Fisher J., Borysiewicz L. K. Subsets of CD8+, CD57+ cells in normal, healthy individuals: correlations with human cytomegalovirus (HCMV) carrier status, phenotypic and functional analyses. Clin Exp Immunol. 1993 Nov;94(2):297–305. doi: 10.1111/j.1365-2249.1993.tb03447.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. d'Angeac A. D., Monier S., Pilling D., Travaglio-Encinoza A., Rème T., Salmon M. CD57+ T lymphocytes are derived from CD57- precursors by differentiation occurring in late immune responses. Eur J Immunol. 1994 Jul;24(7):1503–1511. doi: 10.1002/eji.1830240707. [DOI] [PubMed] [Google Scholar]
  40. de Totero D., Tazzari P. L., DiSanto J. P., di Celle P. F., Raspadori D., Conte R., Gobbi M., Ferrara G. B., Flomenberg N., Lauria F. Heterogeneous immunophenotype of granular lymphocyte expansions: differential expression of the CD8 alpha and CD8 beta chains. Blood. 1992 Oct 1;80(7):1765–1773. [PubMed] [Google Scholar]

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

RESOURCES