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. 1991 Feb 1;173(2):499–502. doi: 10.1084/jem.173.2.499

Expression of perforin and serine esterases by human gamma/delta T cells

PMCID: PMC2118773  PMID: 1703210

Abstract

gamma/delta T cells have recently been described in association with a number of disorders, including autoimmune diseases. gamma/delta T cells are thought to play a cytotoxic role, but their mechanism of action is not known. Several granule mediators of cytotoxicity, including a pore- forming protein (perforin), and a family of serine esterases, have been isolated from cytotoxic T lymphocytes (CTL), lymphokine-activated killer (LAK) cells, and natural killer (NK) cells. We demonstrate here that gamma/delta T cells also express these mediators. Northern blots show that gamma/delta T cells express perforin, serine esterase 1 (SE 1), and SE 2. Three polyclonal antisera - raised against murine perforin, a peptide composed of amino acids 1-34 of human perforin, and human peforin expressed in bacteria - all reacted with a 70-kD protein in gamma/delta T cells on Western blots. Immunostaining with antiperforin antisera shows that primary gamma/delta T cells also contain perforin. Electron microscopy reveals that the granules of gamma/delta T cells resemble those of CTL, LAK, and NK cells. Gamma/delta T cells also resemble LAK cells in possessing inclusion bodies in their nuclei. These results imply that gamma/delta T cells resemble other cytolytic lymphocytes in their mechanism of action.

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Selected References

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  1. Balbi B., Moller D. R., Kirby M., Holroyd K. J., Crystal R. G. Increased numbers of T lymphocytes with gamma delta-positive antigen receptors in a subgroup of individuals with pulmonary sarcoidosis. J Clin Invest. 1990 May;85(5):1353–1361. doi: 10.1172/JCI114579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Carbonari M., Cherchi M., Paganelli R., Giannini G., Galli E., Gaetano C., Papetti C., Fiorilli M. Relative increase of T cells expressing the gamma/delta rather than the alpha/beta receptor in ataxia-telangiectasia. N Engl J Med. 1990 Jan 11;322(2):73–76. doi: 10.1056/NEJM199001113220201. [DOI] [PubMed] [Google Scholar]
  3. Groscurth P., Diener S., Stahel R., Jost L., Kägi D., Hengartner H. Morphologic analysis of human lymphokine-activated killer (LAK) cells. Int J Cancer. 1990 Apr 15;45(4):694–704. doi: 10.1002/ijc.2910450422. [DOI] [PubMed] [Google Scholar]
  4. Henkart P. A. Mechanism of lymphocyte-mediated cytotoxicity. Annu Rev Immunol. 1985;3:31–58. doi: 10.1146/annurev.iy.03.040185.000335. [DOI] [PubMed] [Google Scholar]
  5. Holcombe R. F., van de Griend R., Ang S. L., Bolhuis R. L., Seidman J. G. Gamma-delta T cells in Chediak-Higashi syndrome. Acta Haematol. 1990;83(4):193–197. doi: 10.1159/000205212. [DOI] [PubMed] [Google Scholar]
  6. Holoshitz J., Koning F., Coligan J. E., De Bruyn J., Strober S. Isolation of CD4- CD8- mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid. Nature. 1989 May 18;339(6221):226–229. doi: 10.1038/339226a0. [DOI] [PubMed] [Google Scholar]
  7. Kaufmann S. H. Heat shock proteins and the immune response. Immunol Today. 1990 Apr;11(4):129–136. doi: 10.1016/0167-5699(90)90050-j. [DOI] [PubMed] [Google Scholar]
  8. Liu C. C., Rafii S., Granelli-Piperno A., Trapani J. A., Young J. D. Perforin and serine esterase gene expression in stimulated human T cells. Kinetics, mitogen requirements, and effects of cyclosporin A. J Exp Med. 1989 Dec 1;170(6):2105–2118. doi: 10.1084/jem.170.6.2105. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Liu C. C., Steffen M., King F., Young J. D. Identification, isolation, and characterization of a novel cytotoxin in murine cytolytic lymphocytes. Cell. 1987 Nov 6;51(3):393–403. doi: 10.1016/0092-8674(87)90635-0. [DOI] [PubMed] [Google Scholar]
  10. Modlin R. L., Pirmez C., Hofman F. M., Torigian V., Uyemura K., Rea T. H., Bloom B. R., Brenner M. B. Lymphocytes bearing antigen-specific gamma delta T-cell receptors accumulate in human infectious disease lesions. Nature. 1989 Jun 15;339(6225):544–548. doi: 10.1038/339544a0. [DOI] [PubMed] [Google Scholar]
  11. Ormandy C. J., Clarke C. L., Sutherland R. L. Solubilization and characterization of a lactogenic receptor from human placental chorion membranes. J Cell Biochem. 1990 May;43(1):1–15. doi: 10.1002/jcb.240430102. [DOI] [PubMed] [Google Scholar]
  12. Persechini P. M., Young J. D. The primary structure of the lymphocyte pore-forming protein perforin: partial amino acid sequencing and determination of isoelectric point. Biochem Biophys Res Commun. 1988 Oct 31;156(2):740–745. doi: 10.1016/s0006-291x(88)80905-7. [DOI] [PubMed] [Google Scholar]
  13. Testa U., Care A., Montesoro E., Fossati C., Giannella G., Masciulli R., Fagioli M., Bulgarini D., Habetswallner D., Isacchi G. Interleukin-2-dependent long-term cultures of low-density lymphocytes allow the proliferation of lymphokine-activated killer cells with natural killer, Ti gamma/delta or TNK phenotype. Cancer Immunol Immunother. 1990;31(1):11–18. doi: 10.1007/BF01742490. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Thiele D. L., Lipsky P. E. The role of cell surface recognition structures in the initiation of MHC-unrestricted 'promiscuous' killing by T cells. Immunol Today. 1989 Nov;10(11):375–381. doi: 10.1016/0167-5699(89)90271-5. [DOI] [PubMed] [Google Scholar]
  15. Tschopp J., Jongeneel C. V. Cytotoxic T lymphocyte mediated cytolysis. Biochemistry. 1988 Apr 19;27(8):2641–2646. doi: 10.1021/bi00408a001. [DOI] [PubMed] [Google Scholar]
  16. Young J. D. Killing of target cells by lymphocytes: a mechanistic view. Physiol Rev. 1989 Jan;69(1):250–314. doi: 10.1152/physrev.1989.69.1.250. [DOI] [PubMed] [Google Scholar]
  17. Young L. H., Joag S. V., Zheng L. M., Lee C. P., Lee Y. S., Young J. D. Perforin-mediated myocardial damage in acute myocarditis. Lancet. 1990 Oct 27;336(8722):1019–1021. doi: 10.1016/0140-6736(90)92486-2. [DOI] [PubMed] [Google Scholar]
  18. de Paoli P., Gennari D., Basaglia G., Martelli P., Santini G. Phenotypic analysis of a CD2- CD3+ T cell receptor gamma delta lymphocyte subset. Immunol Lett. 1990 Jan;23(3):195–198. doi: 10.1016/0165-2478(90)90191-r. [DOI] [PubMed] [Google Scholar]

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