Ganz's "Versatile Defensins" 2002

From Biol557

• We know there are defensins in leukocytes and it seems they play a role in directly killing microbes.
• Now there is evidence that they are also important for the anti-HIV activity of CD8+ T lymphocytes and for the induction of cell-mediated immunity.
• One researcher and his work show that stimulated CD8+ T cells of patients who show a long term resistance to the symptoms of HIV secrete alpha-defensins 1, 2, and 3.
• They go on to show that when these defensins are knocked down, HIV is able to infect the host.'
• CAF (CD8 antiviral factor) is also secreted and is known to inhibit infection of cells by HIV through the CD8 cytokine receptor.
• We don't know how the defensins work.
• "Improved understanding of the regulation of defensin production in CD8+ T lymphocytes could potentially extend these benefits to other HIV patients, and eventually a pharmacological substitute for these natural defensins could be developed."
• However, it may be that defensins don't actually provide resistance but are a marker of cells that have been infected but are still capable of sending out resistance-associated molecules. If this is the case, understanding this may help with predicting the best timing for HIV treatment.
• Another set of authors shows that beta-defensins released by neutrophils and epithelial cells not only serves to recruit immature dendritic cells so they can present antigens to T cells but also serves to mature the dendritic cells by binding to their TLRs.
  • In this role, defensins act somewhat like adjuvants in that they stimulate a fuller, faster immune response.
  • Though we might be able to use them in vaccinations or cancer treatments, there is yet doubt because of the large sequence differences in murine and homo sapien defensins.
• Yada, yada, yada.