[Letter to ACT UP Treatment and Data Committee from National Institutes of Health]

Treatment and Data Committee ACT UP

monocyte/macrophages. However, what we are seeing in a single frame picture
of the germinal center may really represent a dynamic process of virus that is
being degraded at the same time that new virus is being deposited on the FDC
processes. Therefore, it is not valid for us to make the conclusion that the
virus is not degraded. We may be just seeing this ongoing process of
degradation followed by redeposition. It is unclear by what mechanisms the T
cells interact with these opsonized viruses. It is conceivable that when CD4+
T cells infiltrate into the germinal center they in fact become infected.
Since we have not formally proven that the HIV on the FDCs can infect
infiltrating T cells, we have undertaken a series of studies where we are
trying to isolate the FDCs from lymph nodes, take the virus off them and
determine if it is still infectious. These studies are ongoing in our
laboratory.
6. A. We do not know what are the events which occur when T cells
infiltrate the germinal centers. We are currently studying programmed cell
death (apoptosis) in these nodes. We do not have any data to report on right
now since we are trying to workout a reproducible system.
B. As mentioned above, there is no formal evidence of direct
infection of HIV from the FDC to the CD4+ T cell.
C. It is entirely conceivable that further infection of nodes
occurs due to circulating CD4+ cells which leave the node and seed other areas
of the lymphoid tissue such as the gut.
D. I do not have the answers to any of the questions in this
subsection. However, we are focusing very heavily on stage dependent changes
in activation phenomenon, viral phenotype, and microenvironment of the node.
I believe that the changes which we see are a combination of a number of
events both cellular as well as viral. However, as you might imagine, it is
logistically very difficult to do these studies, which is the reason why we
are steadfastly pursuing the lymph node work. The questions you ask are
obviously good ones. We will try to answer them one by one.
7. There is no direct evidence to my knowledge to that AZT is taken
up by the lymph node. However, the tissue penetrability of AZT is such that I
would be surprised if it were not taken up by the lymph node.
8. We are currently performing RNA PCR on fractionated subpopulations
of cells in the lymph node to answer precisely the question you ask. We have
gotten the system to be highly reproducible and we are currently looking at
nodes at various stages of disease with regard to the pattern of cytokine
expression.
9. B cells secrete cytokines such as TNF and IL-6 which are potent
inducers of HIV expression. The same can be said of monocytes, which are rich
in cytokine production. Macrophages can get infected with IV and according to
the study by Haase, et al. in Nature, there were monocytes which were infected