1887

Abstract

Deletion of the simian immunodeficiency virus (SIV) gene leads to an attenuated virus phenotype We have previously shown that these viruses induce a potent cellular immune response in macaques. To extend these studies, we established virus-specific short-term T-cell lines from four rhesus macaques infected with a deletion mutant of SIV. These T-cell lines proliferated upon restimulation with whole SIV or SIV gp140 antigen The proliferating cells were characterized as CD4 helper T-cells (TH) and their antigen recognition was MHC class II DR-restricted. After antigenic stimulation, they transcribed mRNA for various TH1- and TH2-like cytokines. Using these SIV-specific cell lines, a variety of helper T-cell epitopes in the SIV Env protein were determined with overlapping peptides. TH epitopes were identified throughout the whole SIV Env including both constant and variable regions. Although the recognition of TH epitopes was heterogeneous among different animals, five more broadly reactive T-cell epitopes were identified. As expected, recognition was associated with the MHC class II background of the animals. This is the first report on helper T-cell epitopes in SIV-infected monkeys. Such studies should be of considerable significance for AIDS/ vaccine research.

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1998-07-01
2022-05-28
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References

  1. Brookes R., Bergmeier L. A., Mitchell E., Walker J., Tao L., Klavinskis L., Meyer N. J., Layton G., Adams S. E., Lehner T. 1995; Generation of diversity in the hierarchy of T-cell epitope responses following different routes of immunisation with simian immunodeficiency virus protein. AIDS 9:1017–1024
    [Google Scholar]
  2. Cohen J. 1997; Weakened SIV vaccine still kills. Science 278:24–25
    [Google Scholar]
  3. Cranage M. P., Cook N., Johnstone P., Greenaway P., Kitchin P. A., Stott E. J., Almond N., Baskerville A. 1990; SIV infection of rhesus macaques: in vitro titration of infectivity and development of an experimental vaccine. In Animal Models in AIDS pp 103–114 Schnellkens H. Edited by Amsterdam: Elsevier;
    [Google Scholar]
  4. Daniel M. D., Kirchhoff F., Czajak S. C., Sehgal P. K., Desrosiers R. C. 1992; Protective effect of a live attenuated SIV vaccine with a deletion in the nef gene. Science 258:1938–1941
    [Google Scholar]
  5. Dittmer U., Lüke W., Stahl-Hennig C., Coulibaly C., Petry H., Bodemer W., Hunsmann G., Voss G. 1994; Early helper T-cell dysfunction in SIV- but not HIV-2-infected macaques. Journal of Medical Primatology 23:21–26
    [Google Scholar]
  6. Dittmer U., Stahl-Hennig C., Coulibaly C., Nißlein T., Lüke W., Wachter H., Fuchs D., Bodemer W., Petry H., Hunsmann G. 1995a; Repeated exposure of rhesus macaques to low doses of simian immunodeficiency virus (SIV) did not protect the animals against the consequences of a high-dose SIV challenge. Journal of General Virology 76:1307–1315
    [Google Scholar]
  7. Dittmer U., Nißlein T., Bodemer W., Petry H., Sauermann U., Stahl-Hennig C., Hunsmann G. 1995b; Cellular immune response of rhesus monkeys infected with a partially attenuated nef deletion mutant of the simian immunodeficiency virus. Virology 212:392–397
    [Google Scholar]
  8. Gallimore A., Cranage M., Cook N., Almond N., Bootman J., Rud E., Silvera P., Dennis M., Corcoran T., Stott J., McMichael A., Gotch F. 1995; Early suppression of SIV replication by CD8 + nef-specific cytotoxic T cells in vaccinated macaques. Nature Medicine 1:1167–1173
    [Google Scholar]
  9. Gundlach B. R., Linhart H., Dittmer U., Sopper S., Reiprich S., Fuchs D., Fleckenstein B., Hunsmann G., Stahl-Hennig C., Überla K. 1997; Construction, replication, and immunological properties of a simian immunodeficiency virus expressing interleukin 2. Journal of Virology 71:2225–2232
    [Google Scholar]
  10. Hu S. L., Abrams K., Barber G. N., Moran P., Zarling J. M., Langlois A. J., Kuller L., Morton W. R., Benveniste R. E. 1992; Protection of macaques against SIV infection by subunit vaccines of SIV envelope glycoprotein gp160. Science 255:456–459
    [Google Scholar]
  11. Jones W. C., Barnard A. L., Slade A., Mills K. H. G. 1992; Heterogeneity in the recognition of the simian immunodeficiency virus envelope glycoprotein by CD4 + T cell clones from immunised macaques. Journal of Immunology 149:3120–3126
    [Google Scholar]
  12. Kestler H. W., Ringler D. J., Mori K., Panicali D. L., Sehgal P. K., Daniel M. D., Desrosiers R. C. 1991; Importance ofthe nef gene for maintenance of high virus loads and for development of AIDS. Cell 65:651–662
    [Google Scholar]
  13. Lehner T., Brookes R., Panagiotidi C., Tao L., Klavinskis L., Walker J., Walker P., Ward R., Hussain L., Gearing A. J. H., Adams S. E., Bergmeier L. A. 1993; T- and B-cell functions and epitope expression in non-human primates immunized with simian immunodeficiency virus SIV Env-specific helper T-cell epitopes antigen by the rectal route. Proceedings of the National Academy of Sciences, USA 90:8638–8642
    [Google Scholar]
  14. Lüke W., Coulibaly C., Dittmer U., Voss G., Oesterle R., Makoschey B., Sauermann U., Jurkiewicz E., Stahl-Hennig C., Petry H., Hunsmann G. 1995; Simian immunodeficiency virus (SIV) gp130 oligomers protect rhesus macaques against the infection with SIVmac32H grown on T-cells or derived ex vivo . Virology 216:444–450
    [Google Scholar]
  15. McBride B. W., Corthals G., Rud E., Kent K., Webster S., Cook N., Cranage M. P. 1993; Comparison of serum antibody reactivities to a conformational and to linear antigenic sites in the external envelope glycoprotein of simian immunodeficiency virus (SIVmac) induced by infection and vaccination. Journal of General Virology 74:1033–1041
    [Google Scholar]
  16. Marthas M. L., Sutjipto S., Higgins J., Lohmann B. L., Torten J., Luciw P. A., Marx P. A., Petersen N. C. 1990; Immunization with a live, attenuated simian immunodeficiency virus (SIV) prevents early disease but not infection in rhesus macaques challenged with pathogenic SIV. Journal of Virology 64:3694–3700
    [Google Scholar]
  17. Mills K. H. G., Jones W. C. 1994; CD4 + T cell responses to simian immunodeficiency viruses. Current Topics in Microbiology and Immunology 188:161–173
    [Google Scholar]
  18. Mills K. H. G., Barnard A. L., Williams M., Page M., Ling C., Stott E. J., Silvera P., Taffs F., Kingsman A. S., Adams S. E., Almond N., Kitchin P. A., Jones W. C. 1991; Vaccine-induced CD4+ T cells against the simian immunodeficiency virus gag protein. Journal of Immunology 147:3560–3567
    [Google Scholar]
  19. Regier D. A., Desrosiers R. C. 1990; The complete nucleotide sequence of a pathogenic molecular clone of simian immunodeficiency virus. AIDS Research and Human Retroviruses 6:1221–1231
    [Google Scholar]
  20. Slierendregt B. L., Otting N., Van Besouw N., Jonker M., Bontrop R. E. 1994; Expansion and contraction of rhesus macaque DRB regions by duplication and deletion. Journal of Immunology 30:2298–2307
    [Google Scholar]
  21. Spring M., Bodemer W., Stahl-Hennig C., Nißlein T., Hunsmann G., Dittmer U. 1997; Impaired mitogen-driven proliferation and cytokine transcription of lymphocytes from macaques early after simian immunodeficiency virus infection. Viral Immunology 10:65–72
    [Google Scholar]
  22. Stahl-Hennig C., Herchenröder O., Nick S., Evers M., Stille-Siegener M., Jentsch K.-D., Kirchhoff F., Tolle T., Gatesmann T. J., Lüke W., Hunsmann G. 1990; Experimental infection of macaques with HIV- 2ben, a novel HIV-2 isolate. AIDS 4:611–617
    [Google Scholar]
  23. Stahl-Hennig C., Dittmer U., Nißlein T., Petry H., Jurkiewicz E., Fuchs D., Wachter H., Mätz-Rensing K., Kuhn E.-M., Kaup F.-J., Rud E. W., Hunsmann G. 1996; Rapid development of vaccine protection in macaques by live-attenuated simian immunodeficiency virus. Journal of General Virology 77:2969–2981
    [Google Scholar]
  24. Voss G., Hunsmann G. 1993; Cellular immune response to SIVmac and HIV-2 in macaques: model for the human HIV-1 infection. Journal of AIDS 6:969–976
    [Google Scholar]
  25. Voss G., Dittmer U., Nick S., Stahl-Hennig C., Coulibaly C., Petry H., Lüke W., Hunsmann G. 1993a; Induction of T-cell proliferation in rhesus macaques immunised with Tween-ether-treated SIVmac and loss of proliferative activity after virus infection. In Animal Models of HIV Infection pp 86–94 Rac P. Edited by Basel: Krager;
    [Google Scholar]
  26. Voss G., Dittmer U., Coulibaly C., Makoschey B., Petry H., Lüke W., Hunsmann G. 1993b; Differences in the B and T cell immune response to the envelope glycoprotein 130 (gp130) of the macaque strain of simian immunodeficiency virus (SIVmac), induced by immunization of rhesus macaques with virus-derived or vaccinia virus-expressed gp130. Journal of General Virology 74:1757–1763
    [Google Scholar]
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