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. 1993 May;61(5):2154–2161. doi: 10.1128/iai.61.5.2154-2161.1993

Listeria monocytogenes-induced gamma interferon secretion by intestinal intraepithelial gamma/delta T lymphocytes.

S Yamamoto 1, F Russ 1, H C Teixeira 1, P Conradt 1, S H Kaufmann 1
PMCID: PMC280816  PMID: 8478105

Abstract

gamma/delta T cells represent a major proportion of intestinal intraepithelial lymphocytes (IEL), and it has been suggested that these IEL serve as a first immune barrier against microbial invasion and that they do so by destroying infected epithelial cells. In the present study, we confirm that both alpha/beta and gamma/delta IEL from naive mice express potent cytotoxicity and produce gamma interferon (IFN-gamma) after T-cell receptor (TCR) engagement by specific monoclonal antibodies (MAb). Intraperitoneal administration of the anti-gamma/delta TCR MAb GL3 caused downregulation of the gamma/delta TCR in IEL, and IEL from gamma/delta TCR-modulated mice failed to express cytotoxic activity and to secrete IFN-gamma after gamma/delta TCR engagement. In contrast, alpha/beta IEL from such mice were still cytolytic and secreted IFN-gamma. Mice were infected orally with virulent Listeria monocytogenes at doses which caused bacterial invasion through the intestinal epithelia. Although alpha/beta and gamma/delta IEL from these mice expressed high cytolytic activities in antibody-redirected killer assays, target cells pulsed with listerial antigens were not lysed. In contrast, IFN-gamma secretion by IEL from L. monocytogenes-infected mice was induced not only by anti-TCR MAb but also by target cells pulsed with listerial antigens, whereas irrelevant antigens, including heat shock protein 60, did not induce IFN-gamma secretion. Furthermore, the number of IFN-gamma-secreting IEL, as assessed by the enzyme-linked immunospot technique, was increased during listeriosis. gamma/delta TCR modulation by GL3 administration abrogated antigen-induced IFN-gamma secretion by IEL from infected mice. These findings suggest that L. monocytogenes induced IFN-gamma secretion by gamma/delta IEL from mice suffering from intestinal L. monocytogenes infection and invasion. Thus, the data provide evidence for a role of IFN-gamma-secreting IEL in local resistance against listeriosis and perhaps other food-borne diseases.

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Selected References

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

  1. Allison J. P., Havran W. L. The immunobiology of T cells with invariant gamma delta antigen receptors. Annu Rev Immunol. 1991;9:679–705. doi: 10.1146/annurev.iy.09.040191.003335. [DOI] [PubMed] [Google Scholar]
  2. Asarnow D. M., Goodman T., LeFrancois L., Allison J. P. Distinct antigen receptor repertoires of two classes of murine epithelium-associated T cells. Nature. 1989 Sep 7;341(6237):60–62. doi: 10.1038/341060a0. [DOI] [PubMed] [Google Scholar]
  3. Barrett T. A., Gajewski T. F., Danielpour D., Chang E. B., Beagley K. W., Bluestone J. A. Differential function of intestinal intraepithelial lymphocyte subsets. J Immunol. 1992 Aug 15;149(4):1124–1130. [PubMed] [Google Scholar]
  4. Bonneville M., Janeway C. A., Jr, Ito K., Haser W., Ishida I., Nakanishi N., Tonegawa S. Intestinal intraepithelial lymphocytes are a distinct set of gamma delta T cells. Nature. 1988 Dec 1;336(6198):479–481. doi: 10.1038/336479a0. [DOI] [PubMed] [Google Scholar]
  5. Goodman T., Lefrancois L. Intraepithelial lymphocytes. Anatomical site, not T cell receptor form, dictates phenotype and function. J Exp Med. 1989 Nov 1;170(5):1569–1581. doi: 10.1084/jem.170.5.1569. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goodman T., Lefrançois L. Expression of the gamma-delta T-cell receptor on intestinal CD8+ intraepithelial lymphocytes. Nature. 1988 Jun 30;333(6176):855–858. doi: 10.1038/333855a0. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Guy-Grand D., Malassis-Seris M., Briottet C., Vassalli P. Cytotoxic differentiation of mouse gut thymodependent and independent intraepithelial T lymphocytes is induced locally. Correlation between functional assays, presence of perforin and granzyme transcripts, and cytoplasmic granules. J Exp Med. 1991 Jun 1;173(6):1549–1552. doi: 10.1084/jem.173.6.1549. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Hahn H., Kaufmann S. H. The role of cell-mediated immunity in bacterial infections. Rev Infect Dis. 1981 Nov-Dec;3(6):1221–1250. doi: 10.1093/clinids/3.6.1221. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Holmgren J., Czerkinsky C., Lycke N., Svennerholm A. M. Mucosal immunity: implications for vaccine development. Immunobiology. 1992 Feb;184(2-3):157–179. doi: 10.1016/S0171-2985(11)80473-0. [DOI] [PubMed] [Google Scholar]
  13. Janssen O., Wesselborg S., Heckl-Ostreicher B., Pechhold K., Bender A., Schondelmaier S., Moldenhauer G., Kabelitz D. T cell receptor/CD3-signaling induces death by apoptosis in human T cell receptor gamma delta + T cells. J Immunol. 1991 Jan 1;146(1):35–39. [PubMed] [Google Scholar]
  14. Kaufmann S. H., Hahn H. Biological functions of t cell lines with specificity for the intracellular bacterium Listeria monocytogenes in vitro and in vivo. J Exp Med. 1982 Jun 1;155(6):1754–1765. doi: 10.1084/jem.155.6.1754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kaufmann S. H. Listeriosis: new findings--current concern. Microb Pathog. 1988 Oct;5(4):225–231. doi: 10.1016/0882-4010(88)90094-0. [DOI] [PubMed] [Google Scholar]
  16. Kaufmann S. H., Rodewald H. R., Hug E., De Libero G. Cloned Listeria monocytogenes specific non-MHC-restricted Lyt-2+ T cells with cytolytic and protective activity. J Immunol. 1988 May 1;140(9):3173–3179. [PubMed] [Google Scholar]
  17. Koga T., Wand-Württenberger A., DeBruyn J., Munk M. E., Schoel B., Kaufmann S. H. T cells against a bacterial heat shock protein recognize stressed macrophages. Science. 1989 Sep 8;245(4922):1112–1115. doi: 10.1126/science.2788923. [DOI] [PubMed] [Google Scholar]
  18. Kubo R. T., Born W., Kappler J. W., Marrack P., Pigeon M. Characterization of a monoclonal antibody which detects all murine alpha beta T cell receptors. J Immunol. 1989 Apr 15;142(8):2736–2742. [PubMed] [Google Scholar]
  19. Kurlander R. J., Shawar S. M., Brown M. L., Rich R. R. Specialized role for a murine class I-b MHC molecule in prokaryotic host defenses. Science. 1992 Jul 31;257(5070):678–679. doi: 10.1126/science.1496381. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Lefrancois L. Phenotypic complexity of intraepithelial lymphocytes of the small intestine. J Immunol. 1991 Sep 15;147(6):1746–1751. [PubMed] [Google Scholar]
  22. Maloy K. J., Mowat A. M., Zamoyska R., Crispe I. N. Phenotypic heterogeneity of intraepithelial T lymphocytes from mouse small intestine. Immunology. 1991 Apr;72(4):555–562. [PMC free article] [PubMed] [Google Scholar]
  23. Mosley R. L., Styre D., Klein J. R. CD4+CD8+ murine intestinal intraepithelial lymphocytes. Int Immunol. 1990;2(4):361–365. doi: 10.1093/intimm/2.4.361. [DOI] [PubMed] [Google Scholar]
  24. Möller S. A., Borrebaeck C. A. A filter immuno-plaque assay for the detection of antibody-secreting cells in vitro. J Immunol Methods. 1985 May 23;79(2):195–204. doi: 10.1016/0022-1759(85)90099-7. [DOI] [PubMed] [Google Scholar]
  25. O'Brien R. L., Fu Y. X., Cranfill R., Dallas A., Ellis C., Reardon C., Lang J., Carding S. R., Kubo R., Born W. Heat shock protein Hsp60-reactive gamma delta cells: a large, diversified T-lymphocyte subset with highly focused specificity. Proc Natl Acad Sci U S A. 1992 May 15;89(10):4348–4352. doi: 10.1073/pnas.89.10.4348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. 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]
  27. Pamer E. G., Wang C. R., Flaherty L., Lindahl K. F., Bevan M. J. H-2M3 presents a Listeria monocytogenes peptide to cytotoxic T lymphocytes. Cell. 1992 Jul 24;70(2):215–223. doi: 10.1016/0092-8674(92)90097-v. [DOI] [PubMed] [Google Scholar]
  28. Prat M., Gribaudo G., Comoglio P. M., Cavallo G., Landolfo S. Monoclonal antibodies against murine gamma interferon. Proc Natl Acad Sci U S A. 1984 Jul;81(14):4515–4519. doi: 10.1073/pnas.81.14.4515. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. 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]
  30. Singh I. G., Mukherjee R., Talwar G. P., Kaufmann S. H. In vitro characterization of T cells from Mycobacterium w-vaccinated mice. Infect Immun. 1992 Jan;60(1):257–263. doi: 10.1128/iai.60.1.257-263.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Spitalny G. L., Havell E. A. Monoclonal antibody to murine gamma interferon inhibits lymphokine-induced antiviral and macrophage tumoricidal activities. J Exp Med. 1984 May 1;159(5):1560–1565. doi: 10.1084/jem.159.5.1560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Taguchi T., Aicher W. K., Fujihashi K., Yamamoto M., McGhee J. R., Bluestone J. A., Kiyono H. Novel function for intestinal intraepithelial lymphocytes. Murine CD3+, gamma/delta TCR+ T cells produce IFN-gamma and IL-5. J Immunol. 1991 Dec 1;147(11):3736–3744. [PubMed] [Google Scholar]
  33. Takagaki Y., DeCloux A., Bonneville M., Tonegawa S. Diversity of gamma delta T-cell receptors on murine intestinal intra-epithelial lymphocytes. Nature. 1989 Jun 29;339(6227):712–714. doi: 10.1038/339712a0. [DOI] [PubMed] [Google Scholar]
  34. Viney J. L., Kilshaw P. J., MacDonald T. T. Cytotoxic alpha/beta+ and gamma/delta+ T cells in murine intestinal epithelium. Eur J Immunol. 1990 Jul;20(7):1623–1626. doi: 10.1002/eji.1830200734. [DOI] [PubMed] [Google Scholar]
  35. Viney J. L., MacDonald T. T., Kilshaw P. J. T-cell receptor expression in intestinal intra-epithelial lymphocyte subpopulations of normal and athymic mice. Immunology. 1989 Apr;66(4):583–587. [PMC free article] [PubMed] [Google Scholar]
  36. Viney J., MacDonald T. T., Spencer J. Gamma/delta T cells in the gut epithelium. Gut. 1990 Aug;31(8):841–844. doi: 10.1136/gut.31.8.841. [DOI] [PMC free article] [PubMed] [Google Scholar]

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