Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1997 May;65(5):1883–1891. doi: 10.1128/iai.65.5.1883-1891.1997

CD95 (Fas) may control the expansion of activated T cells after elimination of bacteria in murine listeriosis.

Y Fuse 1, H Nishimura 1, K Maeda 1, Y Yoshikai 1
PMCID: PMC175236  PMID: 9125576

Abstract

CD95 (Fas) is known to mediate activation-induced T-cell death by apoptosis. To understand the role of CD95 during the course of bacterial infection, we examined the kinetics of alphabeta and gammadelta T cells in the peritoneal cavities and livers of 5-week-old CD95-defective MRL/lpr mice after an intraperitoneal infection with Listeria monocytogenes. The number of bacteria in the spleen decreased to an undetectable level by day 10 after infection with 7 x 10(3) Listeria cells similar to the number in MRL/+/+ mice. The number of alphabeta T cells expressing CD44 and CD95 reached a maximum in the peritoneal cavity on day 6 after listerial infection and thereafter decreased gradually in MRL/+/+ mice, whereas CD44+ alphabeta T cells without CD95 expression continued to increase throughout the course of listerial infection in MRL/lpr mice. Freshly isolated T cells from MRL/+/+ mice infected with L. monocytogenes 10 days previously showed DNA fragmentation with apoptosis, whereas such fragmentation was not prominent in T cells from infected MRL/lpr mice. In correlation with the increased number of CD44+ alphabeta T cells, Listeria-specific T-cell proliferation of peritoneal exudate cells was significantly greater in MRL/lpr mice than in MRL/+/+ mice on day 10 after listerial infection. In contrast to alphabeta T cells, gammadelta T cells increased in number only transiently in the peritoneal cavity and liver after listerial infection in both MRL/lpr mice and MRL/+/+ mice. These results suggest that CD95-mediated cell death with apoptosis may be involved in termination of the alphabeta-T-cell-mediated immune response after the battle against L. monocytogenes has been won, whereas gammadelta T cells may undergo apoptosis independently of CD95 during the course of listerial infection.

Full Text

The Full Text of this article is available as a PDF (577.3 KB).

Selected References

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

  1. Adachi M., Watanabe-Fukunaga R., Nagata S. Aberrant transcription caused by the insertion of an early transposable element in an intron of the Fas antigen gene of lpr mice. Proc Natl Acad Sci U S A. 1993 Mar 1;90(5):1756–1760. doi: 10.1073/pnas.90.5.1756. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Arase H., Ono S., Arase N., Park S. Y., Wakizaka K., Watanabe H., Ohno H., Saito T. Developmental arrest of NK1.1+ T cell antigen receptor (TCR)-alpha/beta+ T cells and expansion of NK1.1+ TCR-gamma/delta+ T cell development in CD3 zeta-deficient mice. J Exp Med. 1995 Sep 1;182(3):891–895. doi: 10.1084/jem.182.3.891. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baldridge J. R., Barry R. A., Hinrichs D. J. Expression of systemic protection and delayed-type hypersensitivity to Listeria monocytogenes is mediated by different T-cell subsets. Infect Immun. 1990 Mar;58(3):654–658. doi: 10.1128/iai.58.3.654-658.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bossu P., Singer G. G., Andres P., Ettinger R., Marshak-Rothstein A., Abbas A. K. Mature CD4+ T lymphocytes from MRL/lpr mice are resistant to receptor-mediated tolerance and apoptosis. J Immunol. 1993 Dec 15;151(12):7233–7239. [PubMed] [Google Scholar]
  5. Camp R. L., Scheynius A., Johansson C., Puré E. CD44 is necessary for optimal contact allergic responses but is not required for normal leukocyte extravasation. J Exp Med. 1993 Aug 1;178(2):497–507. doi: 10.1084/jem.178.2.497. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Conlan J. W., North R. J. Neutrophil-mediated dissolution of infected host cells as a defense strategy against a facultative intracellular bacterium. J Exp Med. 1991 Sep 1;174(3):741–744. doi: 10.1084/jem.174.3.741. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Dhein J., Walczak H., Bäumler C., Debatin K. M., Krammer P. H. Autocrine T-cell suicide mediated by APO-1/(Fas/CD95) Nature. 1995 Feb 2;373(6513):438–441. doi: 10.1038/373438a0. [DOI] [PubMed] [Google Scholar]
  8. Drappa J., Brot N., Elkon K. B. The Fas protein is expressed at high levels on CD4+CD8+ thymocytes and activated mature lymphocytes in normal mice but not in the lupus-prone strain, MRL lpr/lpr. Proc Natl Acad Sci U S A. 1993 Nov 1;90(21):10340–10344. doi: 10.1073/pnas.90.21.10340. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Farr A. G., Kiely J. M., Unanue E. R. Macrophage-T cell interactions involving Listeria monocytogenes--role of the H-2 gene complex. J Immunol. 1979 Jun;122(6):2395–2404. [PubMed] [Google Scholar]
  10. Ferrick D. A., Schrenzel M. D., Mulvania T., Hsieh B., Ferlin W. G., Lepper H. Differential production of interferon-gamma and interleukin-4 in response to Th1- and Th2-stimulating pathogens by gamma delta T cells in vivo. Nature. 1995 Jan 19;373(6511):255–257. doi: 10.1038/373255a0. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. 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]
  13. Harty J. T., Schreiber R. D., Bevan M. J. CD8 T cells can protect against an intracellular bacterium in an interferon gamma-independent fashion. Proc Natl Acad Sci U S A. 1992 Dec 1;89(23):11612–11616. doi: 10.1073/pnas.89.23.11612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Herron L. R., Eisenberg R. A., Roper E., Kakkanaiah V. N., Cohen P. L., Kotzin B. L. Selection of the T cell receptor repertoire in Lpr mice. J Immunol. 1993 Oct 1;151(7):3450–3459. [PubMed] [Google Scholar]
  15. 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]
  16. Inagaki H., Suzuki T., Nomoto K., Yoshikai Y. Increased susceptibility to primary infection with Listeria monocytogenes in germfree mice may be due to lack of accumulation of L-selectin+ CD44+ T cells in sites of inflammation. Infect Immun. 1996 Aug;64(8):3280–3287. doi: 10.1128/iai.64.8.3280-3287.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Itoh N., Yonehara S., Ishii A., Yonehara M., Mizushima S., Sameshima M., Hase A., Seto Y., Nagata S. The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis. Cell. 1991 Jul 26;66(2):233–243. doi: 10.1016/0092-8674(91)90614-5. [DOI] [PubMed] [Google Scholar]
  18. Ju S. T., Panka D. J., Cui H., Ettinger R., el-Khatib M., Sherr D. H., Stanger B. Z., Marshak-Rothstein A. Fas(CD95)/FasL interactions required for programmed cell death after T-cell activation. Nature. 1995 Feb 2;373(6513):444–448. doi: 10.1038/373444a0. [DOI] [PubMed] [Google Scholar]
  19. Kang S. M., Beverly B., Tran A. C., Brorson K., Schwartz R. H., Lenardo M. J. Transactivation by AP-1 is a molecular target of T cell clonal anergy. Science. 1992 Aug 21;257(5073):1134–1138. doi: 10.1126/science.257.5073.1134. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Kawabe Y., Ochi A. Programmed cell death and extrathymic reduction of Vbeta8+ CD4+ T cells in mice tolerant to Staphylococcus aureus enterotoxin B. Nature. 1991 Jan 17;349(6306):245–248. doi: 10.1038/349245a0. [DOI] [PubMed] [Google Scholar]
  22. Klas C., Debatin K. M., Jonker R. R., Krammer P. H. Activation interferes with the APO-1 pathway in mature human T cells. Int Immunol. 1993 Jun;5(6):625–630. doi: 10.1093/intimm/5.6.625. [DOI] [PubMed] [Google Scholar]
  23. Kuroda K., Yagi J., Imanishi K., Yan X. J., Li X. Y., Fujimaki W., Kato H., Miyoshi-Akiyama T., Kumazawa Y., Abe H. Implantation of IL-2-containing osmotic pump prolongs the survival of superantigen-reactive T cells expanded in mice injected with bacterial superantigen. J Immunol. 1996 Aug 15;157(4):1422–1431. [PubMed] [Google Scholar]
  24. Kägi D., Vignaux F., Ledermann B., Bürki K., Depraetere V., Nagata S., Hengartner H., Golstein P. Fas and perforin pathways as major mechanisms of T cell-mediated cytotoxicity. Science. 1994 Jul 22;265(5171):528–530. doi: 10.1126/science.7518614. [DOI] [PubMed] [Google Scholar]
  25. Lenardo M. J. Interleukin-2 programs mouse alpha beta T lymphocytes for apoptosis. Nature. 1991 Oct 31;353(6347):858–861. doi: 10.1038/353858a0. [DOI] [PubMed] [Google Scholar]
  26. Li X. Y., Matsuzaki G., Yoshikai Y., Muramori K., Nomoto K. T cells expressing both L-selectin and CD44 molecules increase in number in peritoneal exudate cells and in vitro-stimulated spleen cells from mice immunized intraperitoneally with Listeria monocytogenes. Immunology. 1993 Jan;78(1):28–34. [PMC free article] [PubMed] [Google Scholar]
  27. Lowin B., Hahne M., Mattmann C., Tschopp J. Cytolytic T-cell cytotoxicity is mediated through perforin and Fas lytic pathways. Nature. 1994 Aug 25;370(6491):650–652. doi: 10.1038/370650a0. [DOI] [PubMed] [Google Scholar]
  28. Mielke M. E., Niedobitek G., Stein H., Hahn H. Acquired resistance to Listeria monocytogenes is mediated by Lyt-2+ T cells independently of the influx of monocytes into granulomatous lesions. J Exp Med. 1989 Aug 1;170(2):589–594. doi: 10.1084/jem.170.2.589. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mogil R. J., Radvanyi L., Gonzalez-Quintial R., Miller R., Mills G., Theofilopoulos A. N., Green D. R. Fas (CD95) participates in peripheral T cell deletion and associated apoptosis in vivo. Int Immunol. 1995 Sep;7(9):1451–1458. doi: 10.1093/intimm/7.9.1451. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Mountz J. D., Baker T. J., Borcherding D. R., Bluethmann H., Zhou T., Edwards C. K., 3rd Increased susceptibility of fas mutant MRL-lpr/lpr mice to staphylococcal enterotoxin B-induced septic shock. J Immunol. 1995 Nov 15;155(10):4829–4837. [PubMed] [Google Scholar]
  32. Murray L. J., Lee R., Martens C. In vivo cytokine gene expression in T cell subsets of the autoimmune MRL/Mp-lpr/lpr mouse. Eur J Immunol. 1990 Jan;20(1):163–170. doi: 10.1002/eji.1830200124. [DOI] [PubMed] [Google Scholar]
  33. Nagata S., Suda T. Fas and Fas ligand: lpr and gld mutations. Immunol Today. 1995 Jan;16(1):39–43. doi: 10.1016/0167-5699(95)80069-7. [DOI] [PubMed] [Google Scholar]
  34. Nishimura Y., Ishii A., Kobayashi Y., Yamasaki Y., Yonehara S. Expression and function of mouse Fas antigen on immature and mature T cells. J Immunol. 1995 May 1;154(9):4395–4403. [PubMed] [Google Scholar]
  35. Ogasawara J., Watanabe-Fukunaga R., Adachi M., Matsuzawa A., Kasugai T., Kitamura Y., Itoh N., Suda T., Nagata S. Lethal effect of the anti-Fas antibody in mice. Nature. 1993 Aug 26;364(6440):806–809. doi: 10.1038/364806a0. [DOI] [PubMed] [Google Scholar]
  36. 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]
  37. Ohteki T., Seki S., Abo T., Kumagai K. Liver is a possible site for the proliferation of abnormal CD3+4-8- double-negative lymphocytes in autoimmune MRL-lpr/lpr mice. J Exp Med. 1990 Jul 1;172(1):7–12. doi: 10.1084/jem.172.1.7. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Otten G. R., Germain R. N. Split anergy in a CD8+ T cell: receptor-dependent cytolysis in the absence of interleukin-2 production. Science. 1991 Mar 8;251(4998):1228–1231. doi: 10.1126/science.1900952. [DOI] [PubMed] [Google Scholar]
  39. Owen-Schaub L. B., Yonehara S., Crump W. L., 3rd, Grimm E. A. DNA fragmentation and cell death is selectively triggered in activated human lymphocytes by Fas antigen engagement. Cell Immunol. 1992 Mar;140(1):197–205. doi: 10.1016/0008-8749(92)90187-t. [DOI] [PubMed] [Google Scholar]
  40. Papiernik M., Pontoux C., Golstein P. Non-exclusive Fas control and age dependence of viral superantigen-induced clonal deletion in lupus-prone mice. Eur J Immunol. 1995 Jun;25(6):1517–1523. doi: 10.1002/eji.1830250607. [DOI] [PubMed] [Google Scholar]
  41. Podack E. R., Hengartner H., Lichtenheld M. G. A central role of perforin in cytolysis? Annu Rev Immunol. 1991;9:129–157. doi: 10.1146/annurev.iy.09.040191.001021. [DOI] [PubMed] [Google Scholar]
  42. Rogers H. W., Callery M. P., Deck B., Unanue E. R. Listeria monocytogenes induces apoptosis of infected hepatocytes. J Immunol. 1996 Jan 15;156(2):679–684. [PubMed] [Google Scholar]
  43. Russell J. H., Rush B., Weaver C., Wang R. Mature T cells of autoimmune lpr/lpr mice have a defect in antigen-stimulated suicide. Proc Natl Acad Sci U S A. 1993 May 15;90(10):4409–4413. doi: 10.1073/pnas.90.10.4409. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sasaki T., Mieno M., Udono H., Yamaguchi K., Usui T., Hara K., Shiku H., Nakayama E. Roles of CD4+ and CD8+ cells, and the effect of administration of recombinant murine interferon gamma in listerial infection. J Exp Med. 1990 Apr 1;171(4):1141–1154. doi: 10.1084/jem.171.4.1141. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Scott D. E., Kisch W. J., Steinberg A. D. Studies of T cell deletion and T cell anergy following in vivo administration of SEB to normal and lupus-prone mice. J Immunol. 1993 Jan 15;150(2):664–672. [PubMed] [Google Scholar]
  46. Singer G. G., Abbas A. K. The fas antigen is involved in peripheral but not thymic deletion of T lymphocytes in T cell receptor transgenic mice. Immunity. 1994 Aug;1(5):365–371. doi: 10.1016/1074-7613(94)90067-1. [DOI] [PubMed] [Google Scholar]
  47. Smathers P. A., Santoro T. J., Chused T. M., Reeves J. P., Steinberg A. D. Studies of lymphoproliferation in MRL-lpr/lpr mice. J Immunol. 1984 Oct;133(4):1955–1961. [PubMed] [Google Scholar]
  48. Smith C. A., Farrah T., Goodwin R. G. The TNF receptor superfamily of cellular and viral proteins: activation, costimulation, and death. Cell. 1994 Mar 25;76(6):959–962. doi: 10.1016/0092-8674(94)90372-7. [DOI] [PubMed] [Google Scholar]
  49. Stalder T., Hahn S., Erb P. Fas antigen is the major target molecule for CD4+ T cell-mediated cytotoxicity. J Immunol. 1994 Feb 1;152(3):1127–1133. [PubMed] [Google Scholar]
  50. Suda T., Nagata S. Purification and characterization of the Fas-ligand that induces apoptosis. J Exp Med. 1994 Mar 1;179(3):873–879. doi: 10.1084/jem.179.3.873. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Van Parijs L., Ibraghimov A., Abbas A. K. The roles of costimulation and Fas in T cell apoptosis and peripheral tolerance. Immunity. 1996 Mar;4(3):321–328. doi: 10.1016/s1074-7613(00)80440-9. [DOI] [PubMed] [Google Scholar]
  52. Vignaux F., Golstein P. Fas-based lymphocyte-mediated cytotoxicity against syngeneic activated lymphocytes: a regulatory pathway? Eur J Immunol. 1994 Apr;24(4):923–927. doi: 10.1002/eji.1830240421. [DOI] [PubMed] [Google Scholar]
  53. Watanabe-Fukunaga R., Brannan C. I., Copeland N. G., Jenkins N. A., Nagata S. Lymphoproliferation disorder in mice explained by defects in Fas antigen that mediates apoptosis. Nature. 1992 Mar 26;356(6367):314–317. doi: 10.1038/356314a0. [DOI] [PubMed] [Google Scholar]
  54. Watanabe-Fukunaga R., Brannan C. I., Itoh N., Yonehara S., Copeland N. G., Jenkins N. A., Nagata S. The cDNA structure, expression, and chromosomal assignment of the mouse Fas antigen. J Immunol. 1992 Feb 15;148(4):1274–1279. [PubMed] [Google Scholar]
  55. Wesselborg S., Janssen O., Kabelitz D. Induction of activation-driven death (apoptosis) in activated but not resting peripheral blood T cells. J Immunol. 1993 May 15;150(10):4338–4345. [PubMed] [Google Scholar]
  56. Zhang L., Miller R. G., Zhang J. Characterization of apoptosis-resistant antigen-specific T cells in vivo. J Exp Med. 1996 May 1;183(5):2065–2073. doi: 10.1084/jem.183.5.2065. [DOI] [PMC free article] [PubMed] [Google Scholar]
  57. Zheng L., Fisher G., Miller R. E., Peschon J., Lynch D. H., Lenardo M. J. Induction of apoptosis in mature T cells by tumour necrosis factor. Nature. 1995 Sep 28;377(6547):348–351. doi: 10.1038/377348a0. [DOI] [PubMed] [Google Scholar]
  58. Zhou T., Bluethmann H., Zhang J., Edwards C. K., 3rd, Mountz J. D. Defective maintenance of T cell tolerance to a superantigen in MRL-lpr/lpr mice. J Exp Med. 1992 Oct 1;176(4):1063–1072. doi: 10.1084/jem.176.4.1063. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES