Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1992 Jul;90(1):204–210. doi: 10.1172/JCI115837

Predominant activation and expansion of V gamma 9-bearing gamma delta T cells in vivo as well as in vitro in Salmonella infection.

T Hara 1, Y Mizuno 1, K Takaki 1, H Takada 1, H Akeda 1, T Aoki 1, M Nagata 1, K Ueda 1, G Matsuzaki 1, Y Yoshikai 1, et al.
PMCID: PMC443082  PMID: 1386086

Abstract

Gamma delta T cell receptor-positive cells (gamma delta T cells) have recently been implicated to play a role in the protection against infectious pathogens. Serial studies on gamma delta T cells in 14 patients with salmonella infection have revealed that the proportions of gamma delta T cells (mean +/- SD: 17.9 +/- 13.2%) in salmonella infection were significantly increased (P less than 0.01) compared with 35 normal controls (5.0 +/- 2.6%) and 13 patients with other bacterial infections (4.0 +/- 1.4%). Expansion of gamma delta T cells was more prominent in the systemic form (28.9 +/- 10.8%) than in the gastroenteritis form (10.5 +/- 7.9%) of salmonella infection (P less than 0.01). Most in vivo-expanded gamma delta T cells expressed V gamma 9 gene product. Increased activated (HLA-DR+) T cells were observed in all the six patients with the systemic form and four of the seven with gastroenteritis form. Especially in the six with systemic form, gamma delta T cell activation was significantly higher than alpha beta T cell activation at the early stage of illness (P less than 0.01). When peripheral blood lymphocytes from normal individuals were cultured with live salmonella, gamma delta T cells were preferentially activated and expanded and most of them expressed V gamma 9. Purified gamma delta T cells also responded to live salmonella in vitro. The present study suggests that human gamma delta T cells play a role in the protection against salmonella infection in vivo.

Full text

PDF
204

Selected References

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

  1. Abo T., Sugawara S., Seki S., Fujii M., Rikiishi H., Takeda K., Kumagai K. Induction of human TCR gamma delta + and TCR gamma delta-CD2+CD3- double negative lymphocytes by bacterial stimulation. Int Immunol. 1990;2(8):775–785. doi: 10.1093/intimm/2.8.775. [DOI] [PubMed] [Google Scholar]
  2. Augustin A., Kubo R. T., Sim G. K. Resident pulmonary lymphocytes expressing the gamma/delta T-cell receptor. Nature. 1989 Jul 20;340(6230):239–241. doi: 10.1038/340239a0. [DOI] [PubMed] [Google Scholar]
  3. Brenner M. B., Strominger J. L., Krangel M. S. The gamma delta T cell receptor. Adv Immunol. 1988;43:133–192. [PubMed] [Google Scholar]
  4. Bucy R. P., Chen C. L., Cooper M. D. Tissue localization and CD8 accessory molecule expression of T gamma delta cells in humans. J Immunol. 1989 May 1;142(9):3045–3049. [PubMed] [Google Scholar]
  5. Carding S. R., Allan W., Kyes S., Hayday A., Bottomly K., Doherty P. C. Late dominance of the inflammatory process in murine influenza by gamma/delta + T cells. J Exp Med. 1990 Oct 1;172(4):1225–1231. doi: 10.1084/jem.172.4.1225. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Chander R., Sainis K. B., Lewis N. F. Role of thymus-derived lymphocytes in acquired immunity to salmonellosis in mice. Microbiol Immunol. 1986;30(12):1299–1306. doi: 10.1111/j.1348-0421.1986.tb03062.x. [DOI] [PubMed] [Google Scholar]
  7. Christmas S. E., Meager A. Production of interferon-gamma and tumour necrosis factor-alpha by human T-cell clones expressing different forms of the gamma delta receptor. Immunology. 1990 Dec;71(4):486–492. [PMC free article] [PubMed] [Google Scholar]
  8. De Libero G., Casorati G., Giachino C., Carbonara C., Migone N., Matzinger P., Lanzavecchia A. Selection by two powerful antigens may account for the presence of the major population of human peripheral gamma/delta T cells. J Exp Med. 1991 Jun 1;173(6):1311–1322. doi: 10.1084/jem.173.6.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. De Paoli P., Gennari D., Martelli P., Cavarzerani V., Comoretto R., Santini G. Gamma delta T cell receptor-bearing lymphocytes during Epstein-Barr virus infection. J Infect Dis. 1990 May;161(5):1013–1016. doi: 10.1093/infdis/161.5.1013. [DOI] [PubMed] [Google Scholar]
  10. Falini B., Flenghi L., Pileri S., Pelicci P., Fagioli M., Martelli M. F., Moretta L., Ciccone E. Distribution of T cells bearing different forms of the T cell receptor gamma/delta in normal and pathological human tissues. J Immunol. 1989 Oct 15;143(8):2480–2488. [PubMed] [Google Scholar]
  11. Faure F., Jitsukawa S., Triebel F., Hercend T. CD3/Ti gamma A: a functional gamma-receptor complex expressed on human peripheral lymphocytes. J Immunol. 1988 Mar 1;140(5):1372–1379. [PubMed] [Google Scholar]
  12. Ferrini S., Zarcone D., Viale M., Cerruti G., Millo R., Moretta A., Grossi C. E. Morphologic and functional characterization of human peripheral blood T cells expressing the T cell receptor gamma/delta. Eur J Immunol. 1989 Jul;19(7):1183–1188. doi: 10.1002/eji.1830190705. [DOI] [PubMed] [Google Scholar]
  13. Fisch P., Malkovsky M., Kovats S., Sturm E., Braakman E., Klein B. S., Voss S. D., Morrissey L. W., DeMars R., Welch W. J. Recognition by human V gamma 9/V delta 2 T cells of a GroEL homolog on Daudi Burkitt's lymphoma cells. Science. 1990 Nov 30;250(4985):1269–1273. doi: 10.1126/science.1978758. [DOI] [PubMed] [Google Scholar]
  14. Gastl G., Niederwieser D., Marth C., Huber H., Egg D., Schuler G., Margreiter R., Braunsteiner H., Huber C. Human large granular lymphocytes and their relationship to natural killer cell activity in various disease states. Blood. 1984 Jul;64(1):288–295. [PubMed] [Google Scholar]
  15. Groh V., Porcelli S., Fabbi M., Lanier L. L., Picker L. J., Anderson T., Warnke R. A., Bhan A. K., Strominger J. L., Brenner M. B. Human lymphocytes bearing T cell receptor gamma/delta are phenotypically diverse and evenly distributed throughout the lymphoid system. J Exp Med. 1989 Apr 1;169(4):1277–1294. doi: 10.1084/jem.169.4.1277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Haas W., Kaufman S., Martinez C. The development and function of gamma delta T cells. Immunol Today. 1990 Oct;11(10):340–343. doi: 10.1016/0167-5699(90)90133-t. [DOI] [PubMed] [Google Scholar]
  17. Hara T., Fu S. M., Hansen J. A. Human T cell activation. II. A new activation pathway used by a major T cell population via a disulfide-bonded dimer of a 44 kilodalton polypeptide (9.3 antigen). J Exp Med. 1985 Jun 1;161(6):1513–1524. doi: 10.1084/jem.161.6.1513. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hara T., Mizuno Y., Nagata M., Okabe Y., Taniguchi S., Harada M., Niho Y., Oshimi K., Ohga S., Yoshikai Y. Human gamma delta T-cell receptor-positive cell-mediated inhibition of erythropoiesis in vitro in a patient with type I autoimmune polyglandular syndrome and pure red blood cell aplasia. Blood. 1990 Feb 15;75(4):941–950. [PubMed] [Google Scholar]
  19. Haregewoin A., Soman G., Hom R. C., Finberg R. W. Human gamma delta+ T cells respond to mycobacterial heat-shock protein. Nature. 1989 Jul 27;340(6231):309–312. doi: 10.1038/340309a0. [DOI] [PubMed] [Google Scholar]
  20. Havlir D. V., Ellner J. J., Chervenak K. A., Boom W. H. Selective expansion of human gamma delta T cells by monocytes infected with live Mycobacterium tuberculosis. J Clin Invest. 1991 Feb;87(2):729–733. doi: 10.1172/JCI115053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hermann E., Mayet W. J., Poralla T., Meyer zum Büschenfelde K. H., Fleischer B. Salmonella-reactive synovial fluid T-cell clones in a patient with post-infectious Salmonella arthritis. Scand J Rheumatol. 1990;19(5):350–355. doi: 10.3109/03009749009096790. [DOI] [PubMed] [Google Scholar]
  22. Ho M., Webster H. K., Tongtawe P., Pattanapanyasat K., Weidanz W. P. Increased gamma delta T cells in acute Plasmodium falciparum malaria. Immunol Lett. 1990 Aug;25(1-3):139–141. doi: 10.1016/0165-2478(90)90105-y. [DOI] [PubMed] [Google Scholar]
  23. Hochadel J. F., Keller K. F. Protective effects of passively transferred immune T- or B-lymphocytes in mice infected with Salmonella typhimurium. J Infect Dis. 1977 May;135(5):813–823. doi: 10.1093/infdis/135.5.813. [DOI] [PubMed] [Google Scholar]
  24. Inoue T., Yoshikai Y., Matsuzaki G., Nomoto K. Early appearing gamma/delta-bearing T cells during infection with Calmétte Guérin bacillus. J Immunol. 1991 Apr 15;146(8):2754–2762. [PubMed] [Google Scholar]
  25. Janis E. M., Kaufmann S. H., Schwartz R. H., Pardoll D. M. Activation of gamma delta T cells in the primary immune response to Mycobacterium tuberculosis. Science. 1989 May 12;244(4905):713–716. doi: 10.1126/science.2524098. [DOI] [PubMed] [Google Scholar]
  26. Kabelitz D., Bender A., Prospero T., Wesselborg S., Janssen O., Pechhold K. The primary response of human gamma/delta + T cells to Mycobacterium tuberculosis is restricted to V gamma 9-bearing cells. J Exp Med. 1991 Jun 1;173(6):1331–1338. doi: 10.1084/jem.173.6.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kabelitz D., Pechhold K., Bender A., Wesselborg S., Wesch D., Friese K., Janssen O. Activation and activation-driven death of human gamma/delta T cells. Immunol Rev. 1991 Apr;120:71–88. doi: 10.1111/j.1600-065x.1991.tb00588.x. [DOI] [PubMed] [Google Scholar]
  28. Kaufmann S. H. Immunity to bacteria. Curr Opin Immunol. 1989;2(3):353–359. doi: 10.1016/0952-7915(89)90141-6. [DOI] [PubMed] [Google Scholar]
  29. Kozbor D., Trinchieri G., Monos D. S., Isobe M., Russo G., Haney J. A., Zmijewski C., Croce C. M. Human TCR-gamma+/delta+, CD8+ T lymphocytes recognize tetanus toxoid in an MHC-restricted fashion. J Exp Med. 1989 May 1;169(5):1847–1851. doi: 10.1084/jem.169.5.1847. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lea T., Smeland E., Funderud S., Vartdal F., Davies C., Beiske K., Ugelstad J. Characterization of human mononuclear cells after positive selection with immunomagnetic particles. Scand J Immunol. 1986 Apr;23(4):509–519. doi: 10.1111/j.1365-3083.1986.tb03083.x. [DOI] [PubMed] [Google Scholar]
  31. Lefrancois L., Goodman T. In vivo modulation of cytolytic activity and Thy-1 expression in TCR-gamma delta+ intraepithelial lymphocytes. Science. 1989 Mar 31;243(4899):1716–1718. doi: 10.1126/science.2564701. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Munk M. E., Gatrill A. J., Kaufmann S. H. Target cell lysis and IL-2 secretion by gamma/delta T lymphocytes after activation with bacteria. J Immunol. 1990 Oct 15;145(8):2434–2439. [PubMed] [Google Scholar]
  34. O'Brien R. L., Happ M. P., Dallas A., Cranfill R., Hall L., Lang J., Fu Y. X., Kubo R., Born W. Recognition of a single hsp-60 epitope by an entire subset of gamma delta T lymphocytes. Immunol Rev. 1991 Jun;121:155–170. doi: 10.1111/j.1600-065x.1991.tb00827.x. [DOI] [PubMed] [Google Scholar]
  35. Ohga S., Yoshikai Y., Takeda Y., Hiromatsu K., Nomoto K. Sequential appearance of gamma/delta- and alpha/beta-bearing T cells in the peritoneal cavity during an i.p. infection with Listeria monocytogenes. Eur J Immunol. 1990 Mar;20(3):533–538. doi: 10.1002/eji.1830200311. [DOI] [PubMed] [Google Scholar]
  36. Paul C., Shalala K., Warren R., Smith R. Adoptive transfer of murine host protection to salmonellosis with T-cell growth factor-dependent, Salmonella-specific T-cell lines. Infect Immun. 1985 Apr;48(1):40–43. doi: 10.1128/iai.48.1.40-43.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Pfeffer K., Schoel B., Gulle H., Kaufmann S. H., Wagner H. Primary responses of human T cells to mycobacteria: a frequent set of gamma/delta T cells are stimulated by protease-resistant ligands. Eur J Immunol. 1990 May;20(5):1175–1179. doi: 10.1002/eji.1830200534. [DOI] [PubMed] [Google Scholar]
  38. Raulet D. H. The structure, function, and molecular genetics of the gamma/delta T cell receptor. Annu Rev Immunol. 1989;7:175–207. doi: 10.1146/annurev.iy.07.040189.001135. [DOI] [PubMed] [Google Scholar]
  39. Roussilhon C., Agrapart M., Ballet J. J., Bensussan A. T lymphocytes bearing the gamma delta T cell receptor in patients with acute Plasmodium falciparum malaria. J Infect Dis. 1990 Jul;162(1):283–285. doi: 10.1093/infdis/162.1.283-a. [DOI] [PubMed] [Google Scholar]
  40. Semenzato G., Pandolfi F., Chisesi T., De Rossi G., Pizzolo G., Zambello R., Trentin L., Agostini C., Dini E., Vespignani M. The lymphoproliferative disease of granular lymphocytes. A heterogeneous disorder ranging from indolent to aggressive conditions. Cancer. 1987 Dec 15;60(12):2971–2978. doi: 10.1002/1097-0142(19871215)60:12<2971::aid-cncr2820601220>3.0.co;2-o. [DOI] [PubMed] [Google Scholar]
  41. Semenzato G., Pizzolo G., Ranucci A., Agostini C., Chilosi M., Quinti I., De Sanctis G., Vercelli B., Pandolfi F. Abnormal expansions of polyclonal large to small size granular lymphocytes: reactive or neoplastic process? Blood. 1984 Jun;63(6):1271–1277. [PubMed] [Google Scholar]
  42. Spencer J., Isaacson P. G., Diss T. C., MacDonald T. T. Expression of disulfide-linked and non-disulfide-linked forms of the T cell receptor gamma/delta heterodimer in human intestinal intraepithelial lymphocytes. Eur J Immunol. 1989 Jul;19(7):1335–1338. doi: 10.1002/eji.1830190728. [DOI] [PubMed] [Google Scholar]
  43. Tagliabue A. Immune response to oral Salmonella vaccines. Curr Top Microbiol Immunol. 1989;146:225–231. doi: 10.1007/978-3-642-74529-4_24. [DOI] [PubMed] [Google Scholar]
  44. Triebel F., Hercend T. Subpopulations of human peripheral T gamma delta lymphocytes. Immunol Today. 1989 Jun;10(6):186–188. doi: 10.1016/0167-5699(89)90321-6. [DOI] [PubMed] [Google Scholar]
  45. Uyemura K., Deans R. J., Band H., Ohmen J., Panchamoorthy G., Morita C. T., Rea T. H., Modlin R. L. Evidence for clonal selection of gamma/delta T cells in response to a human pathogen. J Exp Med. 1991 Sep 1;174(3):683–692. doi: 10.1084/jem.174.3.683. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Vartdal F., Kvalheim G., Lea T. E., Bosnes V., Gaudernack G., Ugelstad J., Albrechtsen D. Depletion of T lymphocytes from human bone marrow. Use of magnetic monosized polymer microspheres coated with T-lymphocyte-specific monoclonal antibodies. Transplantation. 1987 Mar;43(3):366–371. [PubMed] [Google Scholar]
  47. van de Griend R. J., Borst J., Tax W. J., Bolhuis R. L. Functional reactivity of WT31 monoclonal antibody with T cell receptor-gamma expressing CD3+4-8- T cells. J Immunol. 1988 Feb 15;140(4):1107–1110. [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES