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Summary 6 Virus and T cell dynamic in HIV infection
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Summary of the sixth lecture clinical immunology about virus and T cell dynamics in HIV infection
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Clinical Immunology Evelien FloorHC6 Virus and T cell dynamics in HIV infection
The viral load (red) of an HIV infection increases very fast, decreases afterwards and remains for almost
10 years the same. At some moment the equilibrium is lost, and the viral load increases again. People
thought that HIV was a latent virus such as EBV and MHV. However, the amount of virus doesn’t tell
anything about the dynamics: replication. Therefore, viral HIV dynamics was measured.
Dynamics was measured by administering an inhibitor of the HIV protease. Before treatment the viral
load was equal for a long time. From the moment the patient started treatment the viral load declined.
This indicated that replication of HIV in vivo is continuous and highly productive. The half-life of the
virus was only 2 days. So, HIV isn’t a latent virus because there is constant dynamics.
Also, a remarkable CD4+ T cell (blue) decline during HIV infection was measured. It was thought that
the reason for this was that HIV induces death of CD4+ T cells. After investigating this, it was found
that HIV infected cells are not in apoptosis and apoptotic cells are not infected. Another suggestion
was that HIV interferes with thymic output.
Thymic output
Thymic output can be measured by counting T cell receptor excision
circles (TRECs). TRECs are formed during VDJ rearrengemtns in the
thymus. During these rearrangements, DNA is cut out, these pieces of
DNA form stable DNA circles. The number of these TRECs can be
measured inside T cells. A TREC can never be copied, therefore only one
daughter cell receives the TREC during cell division.
Younger individuals have more TRECs in the T cells compared to older
individuals. This is mimicking what is going on in the thymus, in adults
there is less productive tissue producing new T cells. In younger
individuals the T cells are previously formed and therefore more TRECs
are present.
Mathematical model for TREC dynamics
dN/dt is used to describe how the number of cells (N) changes over time. New T cells are produced in
the thymus, during response of infection and there is background proliferation. Cells can be lost
because of apoptosis and differentiation.
The thymus produces an equal number of cells per day (s). In young individuals this is a higher number
than in older individuals (t). Probability to die (d). Chance to proliferate (p).
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