SIV Infection of Follicular Dendritic Cells (FDC) and Other Spleen Cell Subsets in Experimentally Infected Cynomolgus Monkeys
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).
KeywordsGerminal Serine Stein Collagenase
Unable to display preview. Download preview PDF.
- 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.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
- 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.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.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
- 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
- 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.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.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