Follicular Dendritic Cells and Infection by Human Immunodeficiency Virus Type 1—A Crucial Target Cell and Virus Reservoir

Abstract

Even before human immunodeficiency virus type 1 (HIV-1) was recognized as the causative agent of the acquired immunodeficiency syndrome (AIDS), generalized persistent lymphadenopathy was considered as one of the symptoms in this condition. The atypical histologic features of the lymph nodes, mainly the hyperplasia of follicles, were also identified at that time. After the discovery of HIV-1 and the introduction of serology to assess the status of infection, clinicopathologic evaluations could be performed. Schuurman etal. (1985) differentiated three main stages in lymph node abnormalities, which were similar to stages described by Baroni and Uccini (1990) , Biberfeld etal. (1985), Burns etal. (1985) , Garcia etal. (1986) , Janossy etal. (1985), Öst etal. (1989) , Porwit et al. (1989), RÄcz et al. (1986,1990) , and Wood (1990) (Fig. 1):

• 1. Persistent generalized lymphadenopathy develops in the first phase after infection, either as the only symptom or in combination with constitutional symptoms such as persistent fever, weight loss, night-sweat, and diarrhea.

  

  Histology of the swollen lymph nodes shows hyperplasia of the follicles. The follicles not only are large with pronounced germinal centers, but also often show obizarre shape ofgerminal centers with indentations andfragrnentetono ofLhefollicular dendh1iocell (FDC)meshwork. These indentations and fnogmentations are visible in the histologio section as these show the accumulation of small-sized lymphocytes, and not the pale-staining large germinal center cells (Fig. 1 a). The mantle of the follicles is of variable size, and individual follicles can vary from almost absent to quite large. The interfollicular areas in the swollen nodes do not manifest major abnormalities, but can manifest vascular endothelial oeUprolifenstion like that seen inangioirnmunoblestiolymphadenopethy. According to the disease classification by the CENTERS FOR DISEASE CONTROL (CDC; 1988)follicle hyperplasia occurs in either CDC group III (persistent generalized lymphadenopathy) orCDCVA.

• 2. In the subsequent stage, lymphadenopethy is less pronounced. In histology, follicles show a larger extent of fragmentation and degeneration. Some resemblance with angioimrnunoblastiolyrnphedenopathycanbe more evident during the process offollicle degeneration, as visualized byvascular proliferation lymphocyte depletion, end emergence of blastoid cells (Fig. 1b). In CDC subgroups of COC IV when patients have neurologic disease, opportunistic infections, or neoplasia associated with the diagnosis AIDS, lymph nodes show either follicular hyperplasia or follicular degeneration.

• 3. In the last stage, lymph nodes become very small. Histologically, there is follicle atrophy with hyalinizedremnants of the original architecture. Thenode is often depleted of lymphocytes in this terminal stage; plasma cells form one of the main lymphocyte subsets still present inthis stage. Lymph node atrophy is mainly seen in the terminal phase of AIDS.