Abstract
Serial flow cytometry analyses of peripheral blood mononuclear cells obtained from 8 patients infected with Listeria monocytogenes showed a higher percentage (P < 0.01) of gammadelta T cells (median, 11.7; range, 3.7 to 35.3) than did 16 age-matched uninfected controls (1.7, 0.4 to 13). Most in vivo-expanded gammadelta T cells expressed the Vgamma9 and Vdelta2 gene products and displayed a memory phenotype (CD45RO[high]), and patients' gammadelta T cells expressed significantly more (P < 0.01) activation marker HLA-DR than did controls (19.8% [median] and 0.9 to 87.6% [range] versus 2.3% and 0 to 4.7%, respectively). When peripheral blood mononuclear cells from normal donors were cultured in vitro with heat-killed Listeria cells, analysis of CD25 and HLA-DR expression on gammadelta and alphabeta T cells indicated that a high percentage of gammadelta T cells was activated early compared to alphabeta T cells. In addition, depletion of gammadelta T cells before culture abrogated the early lymphocyte proliferative response induced by the pathogen. Taken together, these results argue for the involvement of gammadelta T cells during L. monocytogenes infection in humans.
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- Behr C., Poupot R., Peyrat M. A., Poquet Y., Constant P., Dubois P., Bonneville M., Fournie J. J. Plasmodium falciparum stimuli for human gammadelta T cells are related to phosphorylated antigens of mycobacteria. Infect Immun. 1996 Aug;64(8):2892–2896. doi: 10.1128/iai.64.8.2892-2896.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bertotto A., Gerli R., Spinozzi F., Muscat C., Scalise F., Castellucci G., Sposito M., Candio F., Vaccaro R. Lymphocytes bearing the gamma delta T cell receptor in acute Brucella melitensis infection. Eur J Immunol. 1993 May;23(5):1177–1180. doi: 10.1002/eji.1830230531. [DOI] [PubMed] [Google Scholar]
- Bertotto A., Spinozzi F., Gerli R., Bassotti G., Forenza N., Vagliasindi C., Vaccaro R. Peripheral blood gamma delta T cells in human listeriosis. Acta Paediatr. 1995 Dec;84(12):1434–1435. doi: 10.1111/j.1651-2227.1995.tb13584.x. [DOI] [PubMed] [Google Scholar]
- Constant P., Davodeau F., Peyrat M. A., Poquet Y., Puzo G., Bonneville M., Fournié J. J. Stimulation of human gamma delta T cells by nonpeptidic mycobacterial ligands. Science. 1994 Apr 8;264(5156):267–270. doi: 10.1126/science.8146660. [DOI] [PubMed] [Google Scholar]
- 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]
- De Maria A., Ferrazin A., Ferrini S., Ciccone E., Terragna A., Moretta L. Selective increase of a subset of T cell receptor gamma delta T lymphocytes in the peripheral blood of patients with human immunodeficiency virus type 1 infection. J Infect Dis. 1992 May;165(5):917–919. doi: 10.1093/infdis/165.5.917. [DOI] [PubMed] [Google Scholar]
- Follows G. A., Munk M. E., Gatrill A. J., Conradt P., Kaufmann S. H. Gamma interferon and interleukin 2, but not interleukin 4, are detectable in gamma/delta T-cell cultures after activation with bacteria. Infect Immun. 1992 Mar;60(3):1229–1231. doi: 10.1128/iai.60.3.1229-1231.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fu Y. X., Roark C. E., Kelly K., Drevets D., Campbell P., O'Brien R., Born W. Immune protection and control of inflammatory tissue necrosis by gamma delta T cells. J Immunol. 1994 Oct 1;153(7):3101–3115. [PubMed] [Google Scholar]
- Guo Y., Ziegler H. K., Safley S. A., Niesel D. W., Vaidya S., Klimpel G. R. Human T-cell recognition of Listeria monocytogenes: recognition of listeriolysin O by TcR alpha beta + and TcR gamma delta + T cells. Infect Immun. 1995 Jun;63(6):2288–2294. doi: 10.1128/iai.63.6.2288-2294.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Haas W., Pereira P., Tonegawa S. Gamma/delta cells. Annu Rev Immunol. 1993;11:637–685. doi: 10.1146/annurev.iy.11.040193.003225. [DOI] [PubMed] [Google Scholar]
- Hara T., Mizuno Y., Takaki K., Takada H., Akeda H., Aoki T., Nagata M., Ueda K., Matsuzaki G., Yoshikai Y. Predominant activation and expansion of V gamma 9-bearing gamma delta T cells in vivo as well as in vitro in Salmonella infection. J Clin Invest. 1992 Jul;90(1):204–210. doi: 10.1172/JCI115837. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Harty J. T., Lenz L. L., Bevan M. J. Primary and secondary immune responses to Listeria monocytogenes. Curr Opin Immunol. 1996 Aug;8(4):526–530. doi: 10.1016/s0952-7915(96)80041-0. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hassan J., Feighery C., Bresnihan B., Whelan A. Elevated T cell receptor gamma delta + T cells in patients with infectious mononucleosis. Br J Haematol. 1991 Feb;77(2):255–256. doi: 10.1111/j.1365-2141.1991.tb07990.x. [DOI] [PubMed] [Google Scholar]
- Hiromatsu K., Yoshikai Y., Matsuzaki G., Ohga S., Muramori K., Matsumoto K., Bluestone J. A., Nomoto K. A protective role of gamma/delta T cells in primary infection with Listeria monocytogenes in mice. J Exp Med. 1992 Jan 1;175(1):49–56. doi: 10.1084/jem.175.1.49. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hsieh B., Schrenzel M. D., Mulvania T., Lepper H. D., DiMolfetto-Landon L., Ferrick D. A. In vivo cytokine production in murine listeriosis. Evidence for immunoregulation by gamma delta+ T cells. J Immunol. 1996 Jan 1;156(1):232–237. [PubMed] [Google Scholar]
- Johnson R. M., Lancki D. W., Sperling A. I., Dick R. F., Spear P. G., Fitch F. W., Bluestone J. A. A murine CD4-, CD8- T cell receptor-gamma delta T lymphocyte clone specific for herpes simplex virus glycoprotein I. J Immunol. 1992 Feb 15;148(4):983–988. [PubMed] [Google Scholar]
- Jouen-Beades F., Gilbert D., Ramzaoui S., Borsa-Lebas F., Humbert G., Tron F. Similarity of expression of activation markers and CD28 on gamma delta and alpha beta-receptor T cells in HIV infection. Clin Immunol Immunopathol. 1996 May;79(2):189–193. doi: 10.1006/clin.1996.0066. [DOI] [PubMed] [Google Scholar]
- Kabelitz D., Bender A., Schondelmaier S., Schoel B., Kaufmann S. H. A large fraction of human peripheral blood gamma/delta + T cells is activated by Mycobacterium tuberculosis but not by its 65-kD heat shock protein. J Exp Med. 1990 Mar 1;171(3):667–679. doi: 10.1084/jem.171.3.667. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaufmann S. H. gamma/delta and other unconventional T lymphocytes: what do they see and what do they do? Proc Natl Acad Sci U S A. 1996 Mar 19;93(6):2272–2279. doi: 10.1073/pnas.93.6.2272. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kaur I., Voss S. D., Gupta R. S., Schell K., Fisch P., Sondel P. M. Human peripheral gamma delta T cells recognize hsp60 molecules on Daudi Burkitt's lymphoma cells. J Immunol. 1993 Mar 1;150(5):2046–2055. [PubMed] [Google Scholar]
- Ladel C. H., Blum C., Kaufmann S. H. Control of natural killer cell-mediated innate resistance against the intracellular pathogen Listeria monocytogenes by gamma/delta T lymphocytes. Infect Immun. 1996 May;64(5):1744–1749. doi: 10.1128/iai.64.5.1744-1749.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lang F., Peyrat M. A., Constant P., Davodeau F., David-Ameline J., Poquet Y., Vié H., Fournié J. J., Bonneville M. Early activation of human V gamma 9V delta 2 T cell broad cytotoxicity and TNF production by nonpeptidic mycobacterial ligands. J Immunol. 1995 Jun 1;154(11):5986–5994. [PubMed] [Google Scholar]
- 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]
- Mombaerts P., Arnoldi J., Russ F., Tonegawa S., Kaufmann S. H. Different roles of alpha beta and gamma delta T cells in immunity against an intracellular bacterial pathogen. Nature. 1993 Sep 2;365(6441):53–56. doi: 10.1038/365053a0. [DOI] [PubMed] [Google Scholar]
- 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]
- Nishimura H., Hiromatsu K., Kobayashi N., Grabstein K. H., Paxton R., Sugamura K., Bluestone J. A., Yoshikai Y. IL-15 is a novel growth factor for murine gamma delta T cells induced by Salmonella infection. J Immunol. 1996 Jan 15;156(2):663–669. [PubMed] [Google Scholar]
- 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]
- Parker C. M., Groh V., Band H., Porcelli S. A., Morita C., Fabbi M., Glass D., Strominger J. L., Brenner M. B. Evidence for extrathymic changes in the T cell receptor gamma/delta repertoire. J Exp Med. 1990 May 1;171(5):1597–1612. doi: 10.1084/jem.171.5.1597. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Pfeffer K., Schoel B., Plesnila N., Lipford G. B., Kromer S., Deusch K., Wagner H. A lectin-binding, protease-resistant mycobacterial ligand specifically activates V gamma 9+ human gamma delta T cells. J Immunol. 1992 Jan 15;148(2):575–583. [PubMed] [Google Scholar]
- Rosat J. P., MacDonald H. R., Louis J. A. A role for gamma delta + T cells during experimental infection of mice with Leishmania major. J Immunol. 1993 Jan 15;150(2):550–555. [PubMed] [Google Scholar]
- Roussilhon C., Agrapart M., Guglielmi P., Bensussan A., Brasseur P., Ballet J. J. Human TcR gamma delta+ lymphocyte response on primary exposure to Plasmodium falciparum. Clin Exp Immunol. 1994 Jan;95(1):91–97. doi: 10.1111/j.1365-2249.1994.tb06020.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scalise F., Gerli R., Castellucci G., Spinozzi F., Fabietti G. M., Crupi S., Sensi L., Britta R., Vaccaro R., Bertotto A. Lymphocytes bearing the gamma delta T-cell receptor in acute toxoplasmosis. Immunology. 1992 Aug;76(4):668–670. [PMC free article] [PubMed] [Google Scholar]
- Schoel B., Sprenger S., Kaufmann S. H. Phosphate is essential for stimulation of V gamma 9V delta 2 T lymphocytes by mycobacterial low molecular weight ligand. Eur J Immunol. 1994 Aug;24(8):1886–1892. doi: 10.1002/eji.1830240826. [DOI] [PubMed] [Google Scholar]
- Skeen M. J., Ziegler H. K. Activation of gamma delta T cells for production of IFN-gamma is mediated by bacteria via macrophage-derived cytokines IL-1 and IL-12. J Immunol. 1995 Jun 1;154(11):5832–5841. [PubMed] [Google Scholar]
- Skeen M. J., Ziegler H. K. Induction of murine peritoneal gamma/delta T cells and their role in resistance to bacterial infection. J Exp Med. 1993 Sep 1;178(3):971–984. doi: 10.1084/jem.178.3.971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Takada H., Hiromatsu K., Matsuzaki G., Muramori K., Nomoto K. Peritoneal gamma delta T cells induced by Escherichia coli infection in mice. Correlation between Thy-1 phenotype and host minor lymphocyte-stimulating phenotype. J Immunol. 1993 Aug 15;151(4):2062–2069. [PubMed] [Google Scholar]
- Tsuji M., Mombaerts P., Lefrancois L., Nussenzweig R. S., Zavala F., Tonegawa S. Gamma delta T cells contribute to immunity against the liver stages of malaria in alpha beta T-cell-deficient mice. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):345–349. doi: 10.1073/pnas.91.1.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Yamamoto S., Russ F., Teixeira H. C., Conradt P., Kaufmann S. H. Listeria monocytogenes-induced gamma interferon secretion by intestinal intraepithelial gamma/delta T lymphocytes. Infect Immun. 1993 May;61(5):2154–2161. doi: 10.1128/iai.61.5.2154-2161.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]