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

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 AIDS^2,3. 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).