HIV Is Active in the Lymph Nodes

HIV Is Active in the Lymph Nodes

Although HIV-infected people often show an extended period of clinical latency with little evidence of disease, the virus is never truly completely latent although individual cells may be latently infected. Researchers have shown that even early in disease, HIV actively replicates within the lymph nodes and related organs, where large amounts of virus become trapped in networks of specialized cells with long, tentacle-like extensions. These cells are called follicular dendritic cells (FDCs). FDCs are located in hot spots of immune activity in lymphoid tissue called germinal centers. They act like flypaper, trapping invading pathogens (including HIV) and holding them until B cells come along to start an immune response.

Over a period of years, even when little virus is readily detectable in the blood, significant amounts of virus accumulate in the lymphoid tissue, both within infected cells and bound to FDCs. In and around the germinal centers, numerous CD4+ T cells are probably activated by the increased production of cytokines such as TNF-alpha and IL-6 by immune system cells within the lymphoid tissue. Activation allows uninfected cells to be more easily infected and increases replication of HIV in already infected cells.

While greater quantities of certain cytokines such as TNF-alpha and IL-6 are secreted during HIV infection, other cytokines with key roles in the regulation of normal immune function may be secreted in decreased amounts. For example, CD4+ T cells may lose their capacity to produce IL-2, a cytokine that enhances the growth of other T cells and helps to stimulate other cells' response to invaders. Infected cells also have low levels of receptors for IL-2, which may reduce their ability to respond to signals from other cells.

Breakdown of lymph node architecture

Ultimately, with chronic cell activation and secretion of inflammatory cytokines, the fine and complex inner structure of the lymph node breaks down and is replaced by scar tissue. Without this structure, cells in the lymph node cannot communicate and the immune system cannot function properly. Investigators also have reported recently that this scarring reduces the ability of the immune system to replenish itself following antiretroviral therapy that reduces the viral burden.