Using the Body's Immune System Cells to Achieve Tolerance
There are cells within our own bodies whose job is to constantly scan and rescan the tissues of the body, evaluating what they see. If these cells notice something foreign or out of balance within the body, they have the capacity to trigger the immune system to respond. And in some cases, they have the capacity to suppress a response.
Our scientists are investigating whether this naturally-occurring, continuous process of scanning and reacting could be harnessed to achieve “tolerance.” Could these cells teach the body to either tolerate its own insulin-producing cells or tolerate transplanted insulin-producing cells?
Our scientists are focusing on two types of cells within our own bodies that may be used to re-educate our immune system.
- Marrow Derived Suppressor Cells are naturally occurring cells that accumulate in certain areas of the body. Cancer researchers, for example, know that these MDSCs are present in large numbers around tumors. When the immune system scans the body to inquire about what it needs to attack, it never receives a message from the tumor. The message is suppressed by these cells.
In that case, these Marrow Derived Suppressor Cells inhibit the immune system’s ability to mount an attack against the cancer – essentially, protecting the tumor. But what if we could use MDSCs to protect us for the better – by inhibiting the immune system’s ability to attack transplanted insulin-producing cells?
- Regulatory T Cells are part of the immune system. They regulate the function of the immune system and prevent uncontrolled reactions by suppressing immune responses. This function is particularly important to avoid autoimmune reactions and autoimmune disease, the process whereby the immune system mistakenly attacks its own tissues or cells.
In people with type 1 diabetes, there’s an imbalance of these T Regulatory Cells (Tregs) which leads to the destruction of insulin-producing cells in the pancreas. DRI scientists are developing strategies to restore the balance of T Regulatory Cells. If successful, the rebalancing would allow the immune system to protect against undesirable germs, but would prevent an attack on the insulin-producing cells. We’re currently testing this concept in study models – by infusing transplant recipients with a donor’s T Regulatory Cells prior to islet transplantation.
- Bone Marrow transplantation is commonly used to treat blood-related diseases, such as leukemia. In those instances, the patient’s own cancerous bone marrow is replaced, in its entirety, with marrow from a donor. When this is achieved, it is referred to as "full chimerism."
In other instances, a donor’s transplanted bone marrow may co-exist with a patient’s original marrow. This co-existence is called "mixed chimerism." Researchers here at the DRI have shown that mixed chimerism can be achieved when a transplant recipient accepts bone marrow from the same donor who provides insulin-producing cells. In those cases, the cells are able to exist peacefully - together.
In effect, bone marrow has been used to re-educate the immune system, allowing for this co-existence, or "mixed chimerism" and as a result, an attack against the transplanted insulin-producing cells is prevented.
Leading to a Cure: How This Research Supports Our Mission
The use of T-Regulatory cells may allow us to halt autoimmunity by bringing balance to the immune system. And if Marrow Derived Suppressor Cells can be used to suppress immune responses, transplant recipients may not need to take chronic anti-rejection drugs. In both cases, by using our body’s own cells in a naturally occurring process, we may be able to more safely and effectively achieve our mission to replace insulin function in persons with diabetes.
The use of donor bone marrow cells to achieve a state of "chimerism" may also allow the transplant recipient to discontinue or minimize drug therapy and make the transplant recipient "tolerant" to the new islet cells, yet still allow the immune system to fight off other unwanted invaders. Challenges remain. When bone marrow transplants are used for blood-related diseases, recipients must first undergo harsh pre-conditioning.
The DRI is testing new ways to reduce the recipient’s bone marrow and create space for the donor bone marrow. The group is also defining combinations of drugs that can maximize therapeutic effects, while minimizing unwanted side effects.