Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1996 Dec;70(12):8917–8925. doi: 10.1128/jvi.70.12.8917-8925.1996

Apoptosis by CD95 (Fas)-dependent and -independent mechanisms in Peyer's patch lymphocytes in murine retrovirus-induced immunodeficiency syndrome.

J Usami 1, K Hiromatsu 1, Y Aoki 1, N Kobayashi 1, M Makino 1, H Yagita 1, Y Matsumoto 1, K Maeda 1, Y Yoshikai 1
PMCID: PMC190989  PMID: 8971021

Abstract

CD95 (Fas)/CD95 ligand (CD95 L)-mediated apoptosis is thought to be involved in the delayed progression of murine AIDS (MAIDS) induced by LP-BM5 murine leukemia virus (MuLV). We show evidence of apoptosis in lymphocytes of Peyer's patches (PP) at the early stage of MAIDS. Both T and B cells in PP expressed CD95 at the early stage of MAIDS and decreased in number thereafter. The decrease in T cells was not evident in CD95-mutated lpr mice with MAIDS, suggesting that CD95/CD95 L interaction is involved in the apoptosis of T cells in PP during the course of MAIDS. On the other hand, the number of B cells was also decreased in PP of lpr mice with MAIDS. The proliferative ability of B cells in PP of MAIDS mice in response to immunoglobulin M cross-linking or lipopolysaccharide was severely impaired, while the B cells normally proliferated in response to anti-CD40 monoclonal antibody. These findings imply that aberrantly activated B cells in PP undergo apoptosis independently of the CD95/CD95 L system during the course of infection with MAIDS virus.

Full Text

The Full Text of this article is available as a PDF (943.7 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. Aoki Y., Hiromatsu K., Usami J., Makino M., Igarashi H., Ogasawara J., Nagata S., Yoshikai Y. Clonal expansion but lack of subsequent clonal deletion of bacterial superantigen-reactive T cells in murine retroviral infection. J Immunol. 1994 Oct 15;153(8):3611–3621. [PubMed] [Google Scholar]
  3. Banchereau J., Bazan F., Blanchard D., Brière F., Galizzi J. P., van Kooten C., Liu Y. J., Rousset F., Saeland S. The CD40 antigen and its ligand. Annu Rev Immunol. 1994;12:881–922. doi: 10.1146/annurev.iy.12.040194.004313. [DOI] [PubMed] [Google Scholar]
  4. Brunner T., Mogil R. J., LaFace D., Yoo N. J., Mahboubi A., Echeverri F., Martin S. J., Force W. R., Lynch D. H., Ware C. F. Cell-autonomous Fas (CD95)/Fas-ligand interaction mediates activation-induced apoptosis in T-cell hybridomas. Nature. 1995 Feb 2;373(6513):441–444. doi: 10.1038/373441a0. [DOI] [PubMed] [Google Scholar]
  5. Chattopadhyay S. K., Morse H. C., 3rd, Makino M., Ruscetti S. K., Hartley J. W. Defective virus is associated with induction of murine retrovirus-induced immunodeficiency syndrome. Proc Natl Acad Sci U S A. 1989 May;86(10):3862–3866. doi: 10.1073/pnas.86.10.3862. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cheng G., Cleary A. M., Ye Z. S., Hong D. I., Lederman S., Baltimore D. Involvement of CRAF1, a relative of TRAF, in CD40 signaling. Science. 1995 Mar 10;267(5203):1494–1498. doi: 10.1126/science.7533327. [DOI] [PubMed] [Google Scholar]
  7. Darban H., Enriquez J., Sterling C. R., Lopez M. C., Chen G., Abbaszadegan M., Watson R. R. Cryptosporidiosis facilitated by murine retroviral infection with LP-BM5. J Infect Dis. 1991 Oct;164(4):741–745. doi: 10.1093/infdis/164.4.741. [DOI] [PubMed] [Google Scholar]
  8. Debatin K. M., Fahrig-Faissner A., Enenkel-Stoodt S., Kreuz W., Benner A., Krammer P. H. High expression of APO-1 (CD95) on T lymphocytes from human immunodeficiency virus-1-infected children. Blood. 1994 May 15;83(10):3101–3103. [PubMed] [Google Scholar]
  9. 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]
  10. Durie F. H., Foy T. M., Masters S. R., Laman J. D., Noelle R. J. The role of CD40 in the regulation of humoral and cell-mediated immunity. Immunol Today. 1994 Sep;15(9):406–411. doi: 10.1016/0167-5699(94)90269-0. [DOI] [PubMed] [Google Scholar]
  11. Garrone P., Neidhardt E. M., Garcia E., Galibert L., van Kooten C., Banchereau J. Fas ligation induces apoptosis of CD40-activated human B lymphocytes. J Exp Med. 1995 Nov 1;182(5):1265–1273. doi: 10.1084/jem.182.5.1265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hamann A., Andrew D. P., Jablonski-Westrich D., Holzmann B., Butcher E. C. Role of alpha 4-integrins in lymphocyte homing to mucosal tissues in vivo. J Immunol. 1994 Apr 1;152(7):3282–3293. [PubMed] [Google Scholar]
  13. Hamann A., Jablonski-Westrich D., Jonas P., Thiele H. G. Homing receptors reexamined: mouse LECAM-1 (MEL-14 antigen) is involved in lymphocyte migration into gut-associated lymphoid tissue. Eur J Immunol. 1991 Dec;21(12):2925–2929. doi: 10.1002/eji.1830211205. [DOI] [PubMed] [Google Scholar]
  14. Hartley J. W., Fredrickson T. N., Yetter R. A., Makino M., Morse H. C., 3rd Retrovirus-induced murine acquired immunodeficiency syndrome: natural history of infection and differing susceptibility of inbred mouse strains. J Virol. 1989 Mar;63(3):1223–1231. doi: 10.1128/jvi.63.3.1223-1231.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Hess S., Engelmann H. A novel function of CD40: induction of cell death in transformed cells. J Exp Med. 1996 Jan 1;183(1):159–167. doi: 10.1084/jem.183.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Hiromatsu K., Aoki Y., Makino M., Matsumoto Y., Mizuochi T., Gotoh Y., Nomoto K., Ogasawara J., Nagata S., Yoshikai Y. Increased Fas antigen expression in murine retrovirus-induced immunodeficiency syndrome, MAIDS. Eur J Immunol. 1994 Oct;24(10):2446–2451. doi: 10.1002/eji.1830241028. [DOI] [PubMed] [Google Scholar]
  17. Hitoshi Y., Okada Y., Sonoda E., Tominaga A., Makino M., Suzuki K., Kinoshita J., Komuro K., Mizuochi T., Takatsu K. Delayed progression of a murine retrovirus-induced acquired immunodeficiency syndrome in X-linked immunodeficient mice. J Exp Med. 1993 Mar 1;177(3):621–626. doi: 10.1084/jem.177.3.621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Holzmann B., McIntyre B. W., Weissman I. L. Identification of a murine Peyer's patch--specific lymphocyte homing receptor as an integrin molecule with an alpha chain homologous to human VLA-4 alpha. Cell. 1989 Jan 13;56(1):37–46. doi: 10.1016/0092-8674(89)90981-1. [DOI] [PubMed] [Google Scholar]
  19. Huang M., Simard C., Jolicoeur P. Immunodeficiency and clonal growth of target cells induced by helper-free defective retrovirus. Science. 1989 Dec 22;246(4937):1614–1617. doi: 10.1126/science.2480643. [DOI] [PubMed] [Google Scholar]
  20. Huang M., Simard C., Kay D. G., Jolicoeur P. The majority of cells infected with the defective murine AIDS virus belong to the B-cell lineage. J Virol. 1991 Dec;65(12):6562–6571. doi: 10.1128/jvi.65.12.6562-6571.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Jarry A., Cortez A., René E., Muzeau F., Brousse N. Infected cells and immune cells in the gastrointestinal tract of AIDS patients. An immunohistochemical study of 127 cases. Histopathology. 1990 Feb;16(2):133–140. doi: 10.1111/j.1365-2559.1990.tb01081.x. [DOI] [PubMed] [Google Scholar]
  23. 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]
  24. Kanagawa O., Vaupel B. A., Korsmeyer S. J., Russell J. H. Apoptotic death of lymphocytes in murine acquired immunodeficiency syndrome: involvement of Fas-Fas ligand interaction. Eur J Immunol. 1995 Sep;25(9):2421–2427. doi: 10.1002/eji.1830250902. [DOI] [PubMed] [Google Scholar]
  25. Katsikis P. D., Wunderlich E. S., Smith C. A., Herzenberg L. A., Herzenberg L. A. Fas antigen stimulation induces marked apoptosis of T lymphocytes in human immunodeficiency virus-infected individuals. J Exp Med. 1995 Jun 1;181(6):2029–2036. doi: 10.1084/jem.181.6.2029. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Kawanishi H., Saltzman L. E., Strober W. Mechanisms regulating IgA class-specific immunoglobulin production in murine gut-associated lymphoid tissues. I. T cells derived from Peyer's patches that switch sIgM B cells to sIgA B cells in vitro. J Exp Med. 1983 Feb 1;157(2):433–450. doi: 10.1084/jem.157.2.433. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Kawanishi H., Saltzman L., Strober W. Mechanisms regulating IgA class-specific immunoglobulin production in murine gut-associated lymphoid tissues. II. Terminal differentiation of postswitch sIgA-bearing Peyer's patch B cells. J Exp Med. 1983 Sep 1;158(3):649–669. doi: 10.1084/jem.158.3.649. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Kiyono H., Cooper M. D., Kearney J. F., Mosteller L. M., Michalek S. M., Koopman W. J., McGhee J. R. Isotype specificity of helper T cell clones. Peyer's patch Th cells preferentially collaborate with mature IgA B cells for IgA responses. J Exp Med. 1984 Mar 1;159(3):798–811. doi: 10.1084/jem.159.3.798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Klinman D. M., Morse H. C., 3rd Characteristics of B cell proliferation and activation in murine AIDS. J Immunol. 1989 Feb 15;142(4):1144–1149. [PubMed] [Google Scholar]
  30. Kobayashi N., Hamamoto Y., Yamamoto N., Ishii A., Yonehara M., Yonehara S. Anti-Fas monoclonal antibody is cytocidal to human immunodeficiency virus-infected cells without augmenting viral replication. Proc Natl Acad Sci U S A. 1990 Dec;87(24):9620–9624. doi: 10.1073/pnas.87.24.9620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Krammer P. H., Dhein J., Walczak H., Behrmann I., Mariani S., Matiba B., Fath M., Daniel P. T., Knipping E., Westendorp M. O. The role of APO-1-mediated apoptosis in the immune system. Immunol Rev. 1994 Dec;142:175–191. doi: 10.1111/j.1600-065x.1994.tb00889.x. [DOI] [PubMed] [Google Scholar]
  32. Levy Y., Brouet J. C. Interleukin-10 prevents spontaneous death of germinal center B cells by induction of the bcl-2 protein. J Clin Invest. 1994 Jan;93(1):424–428. doi: 10.1172/JCI116977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Lopez M. C., Colombo L. L., Huang D. S., Watson R. R. Suppressed mucosal lymphocyte populations by LP-BM5 murine leukemia virus infection producing murine AIDS. Reg Immunol. 1992 May-Jun;4(3):162–167. [PubMed] [Google Scholar]
  34. Merino R., Grillot D. A., Simonian P. L., Muthukkumar S., Fanslow W. C., Bondada S., Núez G. Modulation of anti-IgM-induced B cell apoptosis by Bcl-xL and CD40 in WEHI-231 cells. Dissociation from cell cycle arrest and dependence on the avidity of the antibody-IgM receptor interaction. J Immunol. 1995 Oct 15;155(8):3830–3838. [PubMed] [Google Scholar]
  35. Mestecky J., McGhee J. R. Immunoglobulin A (IgA): molecular and cellular interactions involved in IgA biosynthesis and immune response. Adv Immunol. 1987;40:153–245. doi: 10.1016/s0065-2776(08)60240-0. [DOI] [PubMed] [Google Scholar]
  36. Morse H. C., 3rd, Chattopadhyay S. K., Makino M., Fredrickson T. N., Hügin A. W., Hartley J. W. Retrovirus-induced immunodeficiency in the mouse: MAIDS as a model for AIDS. AIDS. 1992 Jul;6(7):607–621. doi: 10.1097/00002030-199207000-00001. [DOI] [PubMed] [Google Scholar]
  37. Mosier D. E., Yetter R. A., Morse H. C., 3rd Functional T lymphocytes are required for a murine retrovirus-induced immunodeficiency disease (MAIDS). J Exp Med. 1987 Jun 1;165(6):1737–1742. doi: 10.1084/jem.165.6.1737. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Mosier D. E., Yetter R. A., Morse H. C., 3rd Retroviral induction of acute lymphoproliferative disease and profound immunosuppression in adult C57BL/6 mice. J Exp Med. 1985 Apr 1;161(4):766–784. doi: 10.1084/jem.161.4.766. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Nagata S., Golstein P. The Fas death factor. Science. 1995 Mar 10;267(5203):1449–1456. doi: 10.1126/science.7533326. [DOI] [PubMed] [Google Scholar]
  40. Núez G., Merino R., Grillot D., González-García M. Bcl-2 and Bcl-x: regulatory switches for lymphoid death and survival. Immunol Today. 1994 Dec;15(12):582–588. doi: 10.1016/0167-5699(94)90221-6. [DOI] [PubMed] [Google Scholar]
  41. Okada Y., Suzuki K., Komuro K., Mizuochi T. High frequency of transmission of murine AIDS virus in C57BL/10 mice via mother's milk. J Virol. 1992 Sep;66(9):5177–5182. doi: 10.1128/jvi.66.9.5177-5182.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Petro T. M., Watson R. R., Feely D. E., Darban H. Suppression of resistance to Giardia muris and cytokine production in a murine model of acquired immune deficiency syndrome. Reg Immunol. 1992 Nov-Dec;4(6):409–414. [PubMed] [Google Scholar]
  43. Rothstein T. L., Wang J. K., Panka D. J., Foote L. C., Wang Z., Stanger B., Cui H., Ju S. T., Marshak-Rothstein A. Protection against Fas-dependent Th1-mediated apoptosis by antigen receptor engagement in B cells. Nature. 1995 Mar 9;374(6518):163–165. doi: 10.1038/374163a0. [DOI] [PubMed] [Google Scholar]
  44. Schrappe-Bächer M., Salzberger B., Fätkenheuer G., Franzen C., Koch B., Krueger G. R., Kaufmann W. T-lymphocyte subsets in the duodenal lamina propria of patients infected with the human immunodeficiency virus type 1 and influence of high-dose immunoglobulin therapy. J Acquir Immune Defic Syndr. 1990;3(3):238–243. [PubMed] [Google Scholar]
  45. Selvey L. A., Morse H. C., 3rd, June C. H., Hodes R. J. Analysis of antigen receptor signaling in B cells from mice with a retrovirus-induced acquired immunodeficiency syndrome. J Immunol. 1995 Jan 1;154(1):171–179. [PubMed] [Google Scholar]
  46. Tsubata T., Wu J., Honjo T. B-cell apoptosis induced by antigen receptor crosslinking is blocked by a T-cell signal through CD40. Nature. 1993 Aug 12;364(6438):645–648. doi: 10.1038/364645a0. [DOI] [PubMed] [Google Scholar]
  47. Wang Z., Karras J. G., Howard R. G., Rothstein T. L. Induction of bcl-x by CD40 engagement rescues sIg-induced apoptosis in murine B cells. J Immunol. 1995 Oct 15;155(8):3722–3725. [PubMed] [Google Scholar]
  48. Westendorp M. O., Frank R., Ochsenbauer C., Stricker K., Dhein J., Walczak H., Debatin K. M., Krammer P. H. Sensitization of T cells to CD95-mediated apoptosis by HIV-1 Tat and gp120. Nature. 1995 Jun 8;375(6531):497–500. doi: 10.1038/375497a0. [DOI] [PubMed] [Google Scholar]
  49. Yetter R. A., Buller R. M., Lee J. S., Elkins K. L., Mosier D. E., Fredrickson T. N., Morse H. C., 3rd CD4+ T cells are required for development of a murine retrovirus-induced immunodeficiency syndrome (MAIDS). J Exp Med. 1988 Aug 1;168(2):623–635. doi: 10.1084/jem.168.2.623. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES