SIV Infection of Follicular Dendritic Cells (FDC) and Other Spleen Cell Subsets in Experimentally Infected Cynomolgus Monkeys

  • Ingrid Stahmer
  • Cosme Ordonez
  • Mikulas Popovic
  • Marianne Ekmman
  • Gunnel Biberfeld
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 378)

Abstract

Follicular dendritic cells (FDC) are localized in primary and secondary lymphoid follicles (germinal center) and are instrumental as antigen presenting cells for the humoral response, particular for the development and maintenance of B-cell memory1. During HIV-1 infection immunohistochemical studies of lymphnode sections revealed that continous destruction of FDC by yet unknown mechanisms was a hallmark of progression to AIDS2,3. We recently could demonstrate that highly purified normal human tonsil FDC were susceptible to HIV-1 infection in vitro in a CD4-independent way4. These findings therefore raised the important question as to the possible in vivo permissivnes of FDC to HIV as an explanation for their destruction during HIV-1 infection. However, although EM studies demonstrated virus budding on FDC membranes in hyperplastic lymph node follicles of HIV-1 infected individuals5, documented histological observations are at present controversial6. Obviously this controversy is related to methodological difficulties of such studies given that the FDC only represent approx. 2% of total germinal center cells7, therefore requiring extensive screening of tissue sections. To overcome this sampling problem we have enriched FDC from spleens of SIVsmm3-infected monkeys (Macaca fascicularis), which have been shown to develop a simian immunodeficiency syndrome with clinical, immunological and pathological hallmarks of human AIDS, including lymphadenopathy and progressive involution of germinal centers8. Spleen FDC from such animals were immunoaffinity enriched and their in vivo permissivnes for viral infection was compared with that of spleen B/T lymphocytes and macrophages (MØ).

Keywords

Germinal Serine Stein Collagenase 

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References

  1. 1.
    G.G.B. Klaus, J.H. Humphrey, A. Kunkl, and D.W. Dongworth, The follicular dendritic cell: its role in antigen presentation in the generation of the immunological memory, Immunol. Rev. 53:3 (1980).PubMedCrossRefGoogle Scholar
  2. 2.
    P. Biberfeld, A. Porwit-Ksiazek, D. Böttiger, L. Morfeldt-Manson, and G. Biberfeld, Lymphadenopathy in HIV infection: histological classification and staging, Cancer Res.45:4665 (1985).Google Scholar
  3. 3.
    P. Racz, K. Tenner-Racz, C. Kahl, A.C. Feller, P. Kern, and M. Dietrich, The spectrum of morphologic changes in lymph nodes from patients with AIDS or AIDS-related complex, Prog Allergy 37:81 (1985).Google Scholar
  4. 4.
    I. Stahmer, J.P. Zimmer, M. Ernst, T. Fenner, R. Finnern, H. Schmitz, H.-D. Flad, and J. Gerdes, Isolation of normal human follicular dendritic cells and CD4-independent in vitro infection by human immunodeficiency virus (HIV-1), Eur. J. Immunol. 21:1873 (1991).PubMedCrossRefGoogle Scholar
  5. 5.
    J.A. Armstrong, D.L. Dawkins, and R. Home, Retroviral infection of accessory cells and the immunological paradox in AIDS, Immunol. Today 6:121 (1985).CrossRefGoogle Scholar
  6. 6.
    J. Embretson, M. Zupancic, J.L. Ribas, A. Burke, P. Racz, K. Tenner-Racz, and A.T. Haase, Massive covert infection of helper T lymphocytes and macrophages by HIV during the incubation period of AIDS, Nature 362:359 (1993).PubMedCrossRefGoogle Scholar
  7. 7.
    N. Cormann, F. Lesage, E. Heinen, N. Schaaf-Lafontaine, C. Kinet-Denoel, and L.J. Simar, Isolation of follicular dendritic cells from human tonsils and adenoids. V. Effect on lymphocyte proliferation and differentiation, Immunol Lett 14:29 (1986/1987)PubMedCrossRefGoogle Scholar
  8. 8.
    P. Putkonen, E. Kaaya, D. Böttiger, S.L. Li, C. Nilsson, P. Biberfeld, and G. Biberfeld, Clinical features and prognostic markers for disease progression in cynomolgus monkeys experimentally infected with simian immunodeficiency virus (SIVsm), AIDS 6:257 (1992).PubMedCrossRefGoogle Scholar
  9. 9.
    P. Putkonen, K. Warstedt, R. Thorstensson, R. Benthin, J. Albert, B. Lundgren, B. Oberg, E. Norrby, and G. Biberfeld, Experimental infection of cynomolgus monkeys (Macaca fascicularis) with simian immuno-deficiency virus (SIVsm), J. Acqu. Imm. Def. Synd. 2:359 (1989).Google Scholar
  10. 10.
    J. Schmitz, S. Petrasch, J. van Lunzen, P. Racz, H.-D. Kleine, F. Hufert, P. Kern, H. Schmitz, and K. Tenner-Racz, Otimizing follicular dendritic cell isolation by discontinous gradient centrifugation and use of the magnetic cell sorter (MACS), J. Immunol. Meth. 159:189 (1993).CrossRefGoogle Scholar
  11. 11.
    J. Gerdes, H. Stein, D.Y. Mason, and A. Ziegler, Human dendritic reticulum cells of lymphoid follicles: their antigenic profile and their identification as multinucleated giant cells, Virch Arch [Cell Pathol] 42:161 (1983).Google Scholar
  12. 12.
    P.U. Cameron, R.L. Dawkins, J.A. Armstrong, and E. Bonifacio, Western blot profiles, lymph node ultrastructure and viral expression in HIV-infected patients: a correlative study, Clin. Exp. Immunol. 68:465 (1987).PubMedGoogle Scholar
  13. 13.
    H.K. Parmentier, D. van Wichen, D.M.D.S. Sie-Go, J. Goudsmit, J.C.C. Borleffs, and H.-J. Schuurman, HIV-1 infection and virus production in follicular dendritic cells in lymph nodes. A case report, with analysis of follicular dendritic cells, Am. J. Path. 137:247 (1990).PubMedGoogle Scholar
  14. 14.
    H. Spiegel, H. Herbst, G. Niedobitek, H.-D. Foss, and H. Stein, Follicular dendritic cells are a major reservoir for human immunodeficiency virus type 1 in lymphoid tissue fascilating infection of CD4+ helper cells, Am. J. Pathol.l40:l5 (1992).Google Scholar
  15. 15.
    L.H.P.M. Rademakers, Dark and light zones of germinal centres of the human tonsil: an ultrasructural study with emphasis on heterogeneity of follicular dendritic cells, Cell Tissue Res. 269:359–(1992).PubMedCrossRefGoogle Scholar
  16. 16.
    B. Odermatt, M. Eppler, T.P. Leist, H. Hengartner, and R.M. Zinkernagel, Virus-triggered acquired immunodeficiency by cytotoxic T-cell-dependent destruction of antigen-presenting cells and lymph follicle structure, Proc. Natl. Acad. Sci. USA 88: 8252–8256 (1991).PubMedCrossRefGoogle Scholar
  17. 17.
    K. Tenner-Racz, P. Racz, C. Thome, C.G. Meyer, P.J. Anderson, S.F. Schlossman, and N.L. Letvin, Cytotoxic effector cell granules recognized by the monoclonal antibody TIA-1 are present in CD8+ lymphocytes in lymph nodes of human immunodeficiency virus-1 infected patients. Am. J. Path. 142 (6): 1750 (1993).PubMedGoogle Scholar
  18. 18.
    P. Joling, H.K. van Wichen, H.K. Parmentier, P. Biberfeld, P, J. Tschopp, and H.-J. Schuurman, Detection of serine esterase granzyme B as indicator of cytotoxic cells in lymphoid follicles in man and cynomolgus monkeys after HIV/SIV infection, In.Cytotoxic T lymphocytes in HIV and other retroviral infections. (P. Racz, N.L. Letvin, J.C. Gluckman, eds., Basel, Karger, 1992), 140.Google Scholar
  19. 19.
    D.W. Frost and A.R. McLean, Germinal center destruction is a major pathway in HIV-1 infection, J. Accqu. Imm. Def. Syndr. 7:236 (1994).Google Scholar

Copyright information

© Springer Science+Business Media New York 1995

Authors and Affiliations

  • Ingrid Stahmer
    • 1
  • Cosme Ordonez
    • 1
  • Mikulas Popovic
    • 2
  • Marianne Ekmman
    • 1
  • Gunnel Biberfeld
    • 3
  1. 1.Immunopathology LabStockholmSweden
  2. 2.Dept. of ImmunologyKarolinska InstituteStockholmSweden
  3. 3.Dept. of ImmunologySwedish Institute for Infectious Disease ControlStockholmSweden

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