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7/29/2010 6:06pm
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One of many immunotolerance mechanisms that immune system has developed to distinguish between self and non-self antigens is regulatory T cells or Tregs.

These cells are recently characterized specialized T-cell subsets that actively suppress a variety of immune responses. Researchers have broadly classified Tregs into natural and adaptive Tregs. Natural Tregs are CD4+CD25+ T-cells that originate in the thymus and play a significant role in immune homeostasis and protection against autoimmunity. Adaptive Tregs are non-regulatory CD4+ T-cells that have up-regulated CD25 expression during pathological and inflammatory conditions such as cancers and infections.

Although the principal immunosuppressive mechanism of Tregs remains elusive, several in vivo experimental models have indicated that Tregs secrete large amounts of immunosuppressants including IL-9, IL-10 and TGF-Beta; upon activation.


These lymphokines are capable of inhibiting activation of Th1, Th2 cells and CTLs required for cell-mediated immunity, inflammation and antibody production. Certain recent experimental data and results even indicate that IL-2-IL-2R signaling is vital for development, maintenance, survival, expansion and suppressive activity of Tregs. Increased expression of certain other characteristic markers including CTLA-4, glucocorticoid-inducible tumor necrosis factor receptor (GITR) and OX40 has been identified on Tregs whose function inside these cells is still not clear. The TCRs displayed on Tregs are capable of recognizing and interacting with any peptide-MHC class II ligand having certain range of avidity. But, the contribution of TCR signaling and role of TCR-ligand interactions towards regulatory T-cell development needs to be determined.


admin - (7/29/2010 - 7:14pm)

Hi Jim

I really appreciate your analysis and your genius. Please keep us informed.

I have read most of your postings and even though I admit to a miniscule understanding of your writings, my gut tells me that you are onto something vitally important.

Do you still subscribe to the importance of the sequencing of ipi and then IL-2 and how do you figure out the timing gap between the administering of the two drugs?

kind regards

miket or talian44

jim Breitfeller - (7/29/2010 - 9:08pm)

The science is coming in loud and clear. Remember I said blame it on the Tregs!!!!! Well Here is some conformation of that.

Tamed T-Cells leave patients cancer-free
Monday, 26 July 2010by Becky Crew

The antigen-specific reaction of T-cells working with dendritic cells, which regulate the immune system.

SYDNEY: The manipulation of specific immune cells in bone marrow transplants has left a number of patients cancer-free, giving new hope to leukemia and lymphoma sufferers, according to a recent study.

A team lead by Sébastien Maury from the Service d'Hématologie Clinique, France, has shown for the first time that by depleting the regulatory T-cell (or Treg) population in donor tissue, patients suffering from very resistant forms of cancer can achieve complete remission.

By identifying the Tregs’ influence on how a new immune system reacts to foreign elements, it’s hoped that this study will result in more successful cancer treatments using transplantation.


This study is proof of a concept which demonstrates that regulatory T-cell manipulation can have therapeutic effects in humans,” says Maury. “It opens the way to its application in various fields in medicine where the immune system needs to be ‘tolerised’ (by adding more regulatory T-cells) in autoimmune diseases or ‘un-tolerised’ (by their elimination) in cancer.”

This Treg manipulation can be accomplished by Ipilimumab. Blocking the CTLA-4 receptor on the Tregs surpressing their tolarance.

JerryfromFauq - (7/2/2011 - 4:24am)

Sounds god.  Now to get more work done to get this line activated in more treatments!

I'm me, not a statistic. Praying to not be one for years yet.