Better Understanding the Outcome of Destroying and Rebuilding the Immune System

The use of chemotherapy to destroy as much of the peripheral immune system as possible, followed by some form of stem cell transplant to rebuild it, has been used for some years as a way to treat multiple sclerosis. In this autoimmune condition, the problem resides in the immune memory, and getting rid of that memory is the solution. The only approach currently demonstrated to work is this somewhat drastic treatment, and the balance of risk and cost means that it is only used for severe diseases such as multiple sclerosis. But in principle, clearance and restoration of the immune system could solve a great many of the issues present in an aged immune system, were there a way to go about it that didn't have the same level of risk and trauma.

Multiple sclerosis (MS) is an autoimmune disease in which the body's own immune system attacks the myelin sheath of the nerve cells in the brain and spinal cord. The disease leads to paralysis, pain, and permanent fatigue, among other symptoms. Fortunately, there have been great advances in therapies in recent decades. 80 percent of patients remain disease-free long-term or even forever following an autologous hematopoietic stem cell transplant. During the treatment, several chemotherapies completely destroy the patients' immune system - including the subset of T cells which mistakenly attack their own nervous system. The patients then receive a transplant of their own blood stem cells, which were harvested before the chemotherapy. The body uses these cells to build a completely new immune system without any autoreactive cells.

Previous studies have shown the basic workings of the method, but many important details and questions remained open. Some unclear aspects were what exactly happens after the immune cells are eliminated, whether any of them survive the chemotherapy, and whether the autoreactive cells really do not return. In a recently published study, researchers systematically investigated these questions for the first time by analyzing the immune cells of 27 MS patients who received stem cell therapy. The analysis was done before, during and up to two years after treatment. This allowed the researchers to track how quickly the different types of immune cells regenerated.

Surprisingly, the cells known as memory T cells, which are responsible for ensuring the body remembers pathogens and can react quickly in case of a new infection, reappeared immediately after the transplant. Further analysis showed that these cells had not re-formed, but had survived the chemotherapy. These remnants of the original immune system nevertheless posed no risk for a return of MS, as they were pre-damaged due to the chemotherapy and therefore no longer able to trigger an autoimmune reaction.

In the months and years following the transplant, the body gradually recreates the different types of immune cells. The thymus gland plays an important role in this process. This is where the T cells learn to distinguish foreign structures, such as viruses, from the body's own. Adults have very little functioning tissue left in the thymus. But after a transplant, the organ appears to resume its function and ensures the creation of a completely new repertoire of T cells which evidently does not trigger MS or cause it to return.



"Adults have very little functioning tissue left in the thymus," says Martin. "But after a transplant, the organ appears to resume its function and ensures the creation of a completely new repertoire of T cells which evidently do not trigger MS or cause it to return."

so could a hsc transplant(in patient without ms) be a way of rejuvenating the thymus?

Posted by: erasmus at November 17th, 2022 5:44 AM

The allogeneic approach with mass produced stem cells will probably win out as it will be a lot cheaper and quicker. Given that, as the study says, it is very difficult to wipe out the original immune system completely, one might well settle for periodic re- treatment with allogeneic stem cells to dilute out the remnants of the original system.

Could be used for a number of diseases in addition to ageing.

Posted by: JLH at November 17th, 2022 1:31 PM

@JLH: can a HSCT be performed without conditioning?

Posted by: erasmus at November 17th, 2022 2:32 PM

By "conditioning" I take it that you mean wiping out the original immune system with XR-chemotherapy.

No essential reason why not, I suppose. Logically far better to eliminate the original immune system first and then repopulate with allogeneic cells, which will then differentiate into a new immune system. Not sure how long this takes. From what I have read , it is quite fast.

Another advantage of allogeneics- they come as a white powder in a vial. One reconstitutes with a diluent and into the patient via IV.

Posted by: JLH at November 17th, 2022 3:15 PM

(above) 2017/02/the-risks-of-current-approaches-to-rebooting-the-immune-system/ > 2016/08/safely-destroying-blood-stem-cells-to-enable-immune-system-restoration/ > "Hematopoietic stem cell transplantation in immunocompetent hosts without radiation or chemotherapy" SciTranslMed (159)

Posted by: Ben (Paris) at November 18th, 2022 6:06 AM
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