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Being Alive
Importance of HIV in Lymph Tissue
Walt Senterfitt
June 5, 1993
Being Alive 1993 Jun 5: 8

Dr. Tony Fauci, a government laboratory scientist and chief of the government's AIDS research, reported in the March 25, 1993 issue of Nature his laboratory's work to date on AIDS pathogenesis. He has been investigating what happens to HIV during the period of clinical latency that sets the stage for the destruction of the immune system.

"Clinical latency" refers to the period between the initial infection with HIV (when virus can be detected in the blood and there are typically flu-like symptoms) and the time several years later when T-cells decline and symptoms eventually appear. In other words, what's going on under the surface during the "healthy asymptomatic stage"? Fauci investigated the lymph nodes taken from HIV+ people at several stages of infection, grouped as early (more than 500 CD4 cells), intermediate (500-200) or advanced (less than 200 T cells) infections. He found that even in early stage, when there is no detectable p24 antigen or viral particles in the blood, there has already begun a hyperplasia (overdevelopment) of the lymph nodes with a host of HIV virions trapped along a mesh-like grid made up of long spindly cells called follicular dendritic cells.

Fauci speculates that this "trapping and holding" process (which is what healthy lymph nodes are supposed to do) helps keep the blood free of virus (a good thing) but may also lure "unsuspecting" T cells into the trap where they can be infected. Many of the trapped cells are coated with immune system proteins and therefore probably cannot be infectious, but no one knows for sure. Even if most of these cells cannot infect, others in the vicinity of the "traps" are vulnerable.

By the intermediate stage, many cells in the lymph node itself have been infected with the virus and probably transmit it to other CD4 cells. Furthermore, the "architecture" of the mesh-containing centers of the lymph nodes has begun to be destroyed. This not only means that fewer HIV virions can be trapped, but also fewer of other types of pathogens. Some HIV is detectable in the blood but not nearly as much as in the lymph nodes.

By the advanced stage, the trapping mechanism has been entirely dissolved. Other lymph node tissue is heavily infected. The virus detectable in the blood stream has come much closer to equalling that in lymph node cells.

Fauci has also investigated the role of early HIV infection in the thymus gland, at least in SCID-Hu mice (who have had their own immune systems destroyed and replaced with human immune cells). The thymus gland is a lymphoid organ essential in the maturation of T-cells, including directing some to become T4, others T8, NK (natural killer) cells and the like. This work is more preliminary but shows that HIV can infect (beginning in an early stage) the T-cells and their precursor stem cells right in the thymus, as well as gradually destroy the nurturing environment necessary for maturation. It's as though HIV invades and trashes the "T-cell nursery." This work is at a beginning stage, but points to the key role of the thymus in early infection and pathogenesis overall.

Fauci also noted that we know that cytokines (the immune system proteins that act as messengers or regulators) play a key role in stimulating HIV replication, even though we don't know all the details. He rhetorically asked, "What could possibly be a more potent generator of cytokines than these activated lymph nodes?" What's the significance of these developments? One thing is finding out quickly whether antiviral drugs have any effect on this HIV trapped in the lymph nodes or invading lymph node cells. Fauci says a lot of data has been collected but in studies still blinded. Another is, researchers must develop ways to assess the effect of any current or new antiviral therapies on HIV in lymph tissue and not just in the bloodstream. This includes more isolated lymph cells in the skin and mucous membranes. Finally, it points to the need for earlier treatment, but with different and better agents than now available. 

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