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Allo-immunization elicits CD8+ T cell-derived chemokines, HIV suppressor factors and resistance to HIV infection in women

Nature Medicine volume 5, pages 1004–1009 (1999)Cite this article

Abstract

We assessed the potential for an allogeneic-based vaccine against HIV infection in women who were allo-immunized with their partners' mononuclear leucocytes to prevent spontaneous recurrent abortion. Within 1 month of allo-immunization, there was significant upregulation in the concentrations of CD8 cell-derived suppressor factor activity, RANTES, and macrophage inflammatory proteins 1α and 1β. Allo-immunization also downregulated the proportion of cells with CCR5 and CXCR4 receptors. We also found a dose-dependent decrease in HIV infectivity of CD4+ cells in vitro after allo-immunization with both primary and T-cell line adapted HIV-1. This study provides a rational basis for an alternative or complementary strategy of allo-immunization against HIV infection.

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Figure 1: The effect of allo-immunization on the level of CD8-SF assayed by inhibition of replication of M- and T-tropic HIV.
Figure 2: Induction of β-chemokines by allo-immunization.
Figure 3: Neutralization of CD8-SF activity with antiserum against β-chemokine.
Figure 4: Percentages of PBMCs expressing CCR5 and CXCR4 receptors were determined by flow cytometry before and about 1 month after immunization in 12 subjects.
Figure 5: The susceptibility of CD4+ cells to infection by four strains of HIV-1.

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References

  1. Mackewicz, C. & Levy, J.A. CD8+ cell anti-HIV activity: Nonlytic suppression of virus replication. AIDS Res. Hum. Retro. 8, 629–640 (1992).

    Article  Google Scholar 

  2. Cocchi, F. et al. Identification of RANTES, MIP-1α and MIP-1β as the major HIV-suppressive factors produced by CD8+ T cells. Science 270, 1811–1815 (1995).

    Article  CAS  Google Scholar 

  3. Lehner, T. et al. Protective mucosal immunity elicited by targeted iliac lymph node immunization with a subunit SIV envelope and core vaccine in macaques. Nature Med. 2, 767–775 (1996).

    Article  CAS  Google Scholar 

  4. Heeney, J. et al. β-chemokines and neutralizing antibody titers correlate with sterilizing immunity generated in HIV vaccinated macaques. Proc. Natl. Acad. Sci. USA 95, 10803–10808 (1998).

    Article  CAS  Google Scholar 

  5. Desrosiers, R.C. et al. Vaccine protection against simian immunodeficiency virus infection. Proc. Natl. Acad. Sci. USA 8, 6353–6357 (1989).

    Article  Google Scholar 

  6. Murphey-Corb, M. et al. Inactivated whole SIV vaccine confers protection in macaques. Science 246, 1293–1247 (1989).

    Article  CAS  Google Scholar 

  7. Carlson, J.R. et al. Vaccine protection of rhesus macaques against simian immunodeficiency virus infection. AIDS Res. Hum. Retroviruses 336, 1239–1246 (1990).

    Article  Google Scholar 

  8. Stott, E.J. et al. Preliminary report: protection of cynomolgus macaques against simian immunodeficiency virus by whole fixed cell vaccine. Lancet 336, 1538–1541 (1990).

    Article  CAS  Google Scholar 

  9. Langlois, A.J., Weinhold, K.J., Matthews, T.J., Greenberg, M.L. & Bolognes, D.P. The ability of certain SIV vaccines to provoke reactions against normal cells. Science 255, 292–293 (1992).

    Article  CAS  Google Scholar 

  10. Arthur, L.O. et al. Cellular proteins bound to immunodeficiency viruses: implications for pathogenesis and vaccines. Science 258, 1935–1938 (1992).

    Article  CAS  Google Scholar 

  11. Stott, E.J. et al. Anti-cell antibody in macaques. Nature 353, 393 (1991).

    Article  CAS  Google Scholar 

  12. Stott J. et al. Protection against simian immunodeficiency virus infection of macaques by cellular or viral antigens. Neuvieme Colloque des Cent Gardes 1994, 219–224 (1994).

  13. Wang, Y. et al. Generation of CD8-SF and β-chemokines, induced by xenogeneic immunization, in the prevention of SIV infection in macaques. Proc. Natl. Acad. Sci. USA 95, 5223–5228 (1998).

    Article  CAS  Google Scholar 

  14. Shearer, G.M., Clerici, M. & Dalgleish, A. Alloimmunization as an AIDS vaccine? Science 262, 161–162 (1993).

    Article  CAS  Google Scholar 

  15. Clerici, M. et al. Alloactivated cytotoxic T cells recognize the carboxy-terminal domain of human immunodeficiency virus-1 gp120 envelope glycoprotein. Eur. J. Immunol. 23, 2022–2025 (1993).

    Article  CAS  Google Scholar 

  16. Bruhl, P., Kerschbaum, A., Zimmermann, K., Eibl, M.M. & Mannhalter, J.W. Allostimulated lymphocytes inhibit replication of HIV type 1. AIDS Res. Hum. Retroviruses 12, 31–37 (1996).

    Article  CAS  Google Scholar 

  17. Mowbray, J.F., Underwood, J.L., Michel, M., Forbes, P.B. & Beard, R.W. Immunization with paternal lymphocytes in women with recurrent miscarriage. Lancet ii, 679–680 (1987).

    Article  Google Scholar 

  18. Bunce, M., Barnardo, M.C., Procter, J., Marsh, S.G., Vilches, C. & Welsh, K.I. High resolution HLA-C typing by PCR-SSP: identification of allelic frequencies and linkage disequilibria in 604 unrelated random UK Caucasoids and a comparison with serology. Tissue Antigens 50, 100–111 (1997).

    Article  CAS  Google Scholar 

  19. Kishore, R., Agarrwal, S., Halder, A., Das, V., Shukla, B.R. & Agarwal, S.S. HLA sharing, anti-paternal cytotoxic antibodies and MLR blocking factors in women with recurrent spontaneous abortion. J. Obstet. Gynaecol. Res. 22, 177–183 (1996).

    Article  CAS  Google Scholar 

  20. Cocchi, F., DeVico, A.L., Garzino-Demo, A., Cara, A., Gallo, R.C. & Lusso, P. The V3 domain of the HIV gp120 envelope glycoprotein is critical for chemokine- mediated blockade of infection. Nature Med. 2, 1244–1247 (1996).

    Article  CAS  Google Scholar 

  21. Dragic, T. et al. HIV-1 entry into CD4+ cells is mediated by the chemokine receptor CC-CKR-5. Nature 381, 667–673 (1996).

    Article  CAS  Google Scholar 

  22. Deng, H. et al. Identification of a major co-receptor for primary isolates of HIV-1. Nature 381, 661–666 (1996).

    Article  CAS  Google Scholar 

  23. Feng, Y., Broder, C.C., Kennedy, P.E. & Berger, E.A. HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science 272, 872–877 (1996).

    Article  CAS  Google Scholar 

  24. Dean, M. et al. Genetic restriction of HIV infection and progression to AIDS by a deletion allele of the CKR5 structual gene. Science 273, 1856–1862 (1996).

    Article  CAS  Google Scholar 

  25. Liu, R. et al. Homozygous defect in HIV-1 co-receptor accounts for resistance of some multiply-exposed individuals to HIV infection. Cell 86, 367–377 (1996).

    Article  CAS  Google Scholar 

  26. Samson, M. et al. Resistance to HIV-1 infection in caucasian individuals bearing mutant alleles of the CCR-5 chemokine receptor gene. Nature 382, 722–725 (1996).

    Article  CAS  Google Scholar 

  27. Amara, A. et al. HIV coreceptor downregulation as antiviral principle: SDF-1α-dependent internalization of the chemokine receptor CXCR4 contributes to inhibition of HIV replication. J. Exp. Med. 186, 139–146 (1997).

    Article  CAS  Google Scholar 

  28. Wu, J. et al. CCR5 levels and expression pattern correlate with infectability by macrophage-tropic HIV-1, in vitro. J. Exp. Med. 186, 1681–1691 (1997).

    Article  Google Scholar 

  29. Simmons, G. et al. Primary, syncytium-inducing human immunodeficiency virus type 1 isolates are dual-tropic and most can use either Lestr or CCR5 as coreceptors for virus entry. J. Virol. 70, 8355–8360 (1996).

    CAS  PubMed  PubMed Central  Google Scholar 

  30. Paxton, W. et al. Relative resistant to HIV-1 infection of CD4 lymphocytes from persons who remain uninfected despite multiple high-risk sexual exposures. Nature Med. 2, 412–417 (1996).

    Article  CAS  Google Scholar 

  31. Pinto, L.A., Sharpe, S., Cohen, D.I. & Shearer, G.M. Alloantigen-stimulated anti-HIV activity. Blood 92, 3346–3354 (1998).

    CAS  PubMed  Google Scholar 

  32. Moriuchi, H., Moriuchi, M. & Fauci, A.S. Induction of HIV-1 replication by allogeneic stimulation. J. Immunol. 162, 7543–7548 (1999).

    CAS  PubMed  Google Scholar 

  33. Tachibana K. et al. The chemokine receptor CXCR4 is essential for vascularization of the gastrointestinal tract. Nature 393, 591–594 (1998).

    Article  CAS  Google Scholar 

  34. Zhou, Y., Kottmann, A.H., Kuroda, M., Taniuchi, I. & Littman D.R. Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature 393, 595–599 (1998).

    Article  Google Scholar 

  35. Plummer,F.A. et al. Evidence of resistance to HIV among continuously exposed prostitutes in Nairobi, Kenya. >Program and Abstracts: IXth Int. Conf. AIDS/HIV STD World Congress Abstract WS, A07-3 (Berlin, 1993).

  36. Celum, C.L. et al. Risk factors for repeatedly reactive HLA-1 EIA and indeterminate western blot. A population-based case-control study. Arch. Intern. Med. 154, 1129–1137 (1994).

    Article  CAS  Google Scholar 

  37. Kind, C. Mother-to-child transmission of human immunodeficiency virus type 1: influence of parity and mode of delivery. Eur. J. Pediatr. 154, 542–545 (1995).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported partly by grants from the European Community Concerted Action Against AIDS (CT 960450), the National Institute of Acquired Immunodeficiency Disease, Washington, DC, and Guy's Special Trustees.

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Authors and Affiliations

  1. Department of Immunobiology, Guy's, King's and St. Thomas' Medical and Dental Schools at Guy's Hospital, Medical School Building, 3rd Floor, London, SE1 9RT, UK

    Yufei Wang, Louisa Tao, Elaine Mitchell, Christopher Bravery & Thomas Lehner

  2. Department of Tissue Typing, Guy's, King's and St. Thomas' Medical and Dental Schools at Guy's Hospital, Medical School Building, 3rd Floor, London, SE1 9RT, UK

    Pasqule Berlingieri & Paul Armstrong

  3. Department of Gynaecology, Royal London Hospital, Turner Street, E1 2AD, England

    Robert Vaughan

  4. Department of Obstetrics and Gynaecology, Imperial College, St. Mary's Hospital Medical Faculty, Norfolk Place, London, W2 1PG, UK

    Jenny Underwood

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  1. Yufei Wang
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Correspondence to Thomas Lehner.

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Wang, Y., Tao, L., Mitchell, E. et al. Allo-immunization elicits CD8+ T cell-derived chemokines, HIV suppressor factors and resistance to HIV infection in women. Nat Med 5, 1004–1009 (1999). https://doi.org/10.1038/12440

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