Follicular dendritic cells are a major reservoir for human immunodeficiency virus type 1 in lymphoid tissues facilitating infection of CD4+ T-helper cells.
Human immunodeficiency virus type 1 (HIV-1) infection causes progressive depletion of CD4/HIV-receptor-positive T helper lymphocytes, ultimately leading to AIDS. The major HIV reservoir and site of T-helper cell infection in lymphoid tissues, however, has remained poorly defined. The authors used in situ hybridization in combination with immunohistologic labeling techniques to identify the phenotype of HIV-infected cells in lymph nodes from patients at different stages of HIV-infection. The number of HIV-infected macrophages, widely considered the major site of HIV replication, was extremely low. There was no evidence for HIV-infection of endothelial and interdigitating reticulum cells. However, HIV RNA was found in small but consistent proportions of CD45RO-positive T cells and in the vast majority of follicular dendritic cells (FDC) in a pattern suggestive of active infection in addition to HIV-immunocomplex trapping on cell membranes. FDC may therefore be a major HIV reservoir and since T-helper cells travel through the FDC meshwork during their migration within lymphoreticular tissues, it appears likely that HIV-replicating T cells may infect FDC, which then infect new T cells, thus causing a gradual dissemination of the virus to all FDC and thereby a steadily increasing infection of T-helper/memory cells within germinal centers. This results in CD4+ T cell depletion, and ultimately, in immunodeficiency.
Spiegel
H
H
Institute of Pathology, Klinikum Steglitz, Free University Berlin, Federal Republic of Germany.
Herbst
H
H
Niedobitek
G
G
Foss
H D
HD
Stein
H
H
D000328:Adult; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens / Q000032:analysis*; D003713:Dendritic Cells / Q000737:chemistry / Q000382:microbiology* / Q000473:pathology; D005260:Female; D015658:HIV Infections / Q000276:immunology / Q000473:pathology; D015497:HIV-1 / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007150:Immunohistochemistry; D007223:Infant; D008212:Lymphocyte Depletion; D008221:Lymphoid Tissue / Q000737:chemistry / Q000382:microbiology* / Q000473:pathology; D008297:Male; D009693:Nucleic Acid Hybridization; D010641:Phenotype; D012367:RNA, Viral / Q000032:analysis / Q000235:genetics; D006377:T-Lymphocytes, Helper-Inducer / Q000737:chemistry / Q000276:immunology / Q000382:microbiology*
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D012367:RNA, Viral