THE concept of tumour surveillance implies that specific and nonspecific components of the immune system eliminate tumours in the early phase of malignancy1,2. The immunological mechanisms that control growth of preneoplastic cells are, however, not known. T cells expressing γδ T-cell receptors (TCR) were first described as lymphocytes with reactivity against various tumour cells, which suggests that γδ T cells could mediate tumour surveillance3–6. Here we show that TCRVγ1.1Jγ4Cγ4 transgenic mice7 are spontaneously resistant to acute T-cell leukaemias but cannot reject non-haematopoietic tumours. TCRVγ1.1Jγ4Cγ4+ hybridomas isolated from these mice react in vitro against almost all haematopoietic tumour cell lines tested. Recognition of tumour cells depends on the γδ TCR but is independent of major histocompati-bility complex (MHC) class I, MHC class II, or TAP-2 peptide transporter expression. Ligand recognition is influenced by the murine Nromp gene, which confers resistance or susceptibility to tuberculosis, lepra and leishmaniasis8,9. These data indicate that TCRVγ1.1+ T cells confer spontaneous immunity against haematopoietic tumours in vivo and link innate resistance to bacterial infections with tissue-specific tumour surveillance by γδ+ T cells.
Subscribe to Journal
Get full journal access for 1 year
only $3.90 per issue
All prices are NET prices.
VAT will be added later in the checkout.
Rent or Buy article
Get time limited or full article access on ReadCube.
All prices are NET prices.
Klein, G. & Boon, T. Curr. Opin. Immun. 5, 687–692 (1993).
Pardoll, D. M. Curr. Opin. Immun. 5, 719–725 (1993).
Haas, W., Pereira, P. & Tonegawa, S. A. Rev. Immun. 11, 637–686 (1993).
Allison, J. P. & Havran, W. L. A. Rev. Immun. 9, 679–705 (1991).
Raulet D. H. A. Rev. Immun. 7, 175–207 (1989).
Kronenberg, M. Curr. Opin. Immun. 6, 64–71 (1994).
Ferrick, D. A. et al. Cell 57, 483–492 (1989).
Radzioch, D. et al. J. Leuk. Biol. 50, 263–270 (1991).
Vidal, S. M., Malo, D., Vogan, K., Skamene, E. & Gros, P. Cell 73, 469–485 (1993).
Correa, I. et al. Proc. natn. Acad. Sci. U.S.A. 89, 653–657 (1992).
Schild, H. et al. Cell 76, 29–37 (1994).
Kärre, K., Ljunggren, H. G., Piontek, G. & Kiessling, R. Nature 319, 675–678 (1986).
O'Brien, R. L. et al. Cell 57, 667–674 (1989).
Yeung, R. A. & Elliot, T. J. Cell 59, 5–8 (1989).
Silva, C. L., Lukacs, K. & Lowrie, D. B. Immunology 78, 35–42 (1993).
Born, W. et al. Science 249, 67–69 (1990).
Munk, M. E., Gatrill, A. J. & Kaufmann, S. H. E. J. Immun. 145, 2434–2439 (1990).
Mombaerts, P., Arnoldi, J., Russ, F., Tonegawa, S. & Kaufmann, S. H. E. Nature 365, 53–56 (1993).
Kabelitz, D. et al. J. exp. Med. 173, 1331–1338 (1991).
De Libero, G. et al. J. exp. Med. 173, 1311–1322 (1991).
Uyemura, K. et al. J. exp. Med. 174, 683–692 (1992).
Barton, C. H., White, J. K., Roach, T. I. A. & Blackwell, J. M. J. exp. Med. 179, 1683–1687 (1994).
Nathan, C. FASEB J. 6, 3051–3061 (1992).
About this article
Cite this article
Penninger, J., Wen, T., Timms, E. et al. Spontaneous resistance to acute T-cell leukaemias in TCRVγ1.1Jγ4Cγ4 transgenic mice. Nature 375, 241–244 (1995) doi:10.1038/375241a0
Reconstitution of T and NK cells after haploidentical hematopoietic cell transplantation using αβ T cell-depleted grafts and the clinical implication of γδ T cells
Clinical Transplantation (2018)
Selective, efficient modulation of activated CD4+ αβT cells by the novel humanized antibody GZ-αβTCR targeting human αβTCR
Bone Marrow Transplantation (2015)
PLoS Pathogens (2010)
Cancer Biotherapy and Radiopharmaceuticals (2007)
Immunomodulating role of bisphosphonates on human gamma delta T cells: an intriguing and promising aspect of their antitumour activity
Expert Opinion on Therapeutic Targets (2007)