News & Research

    Beth Israel Deaconess Medical Center, Boston, Massachusetts

Danger in the creation of tolerance

General Research Subject: Both Type 1 And Type 2 Diabetes

Focus: Immunology, Other, Transplantation

Type of Grant: Basic Science

Project Start Date: January 1, 2013

Project End Date: December 31, 2015

Research Description

Immune cells take cues from the environment in which they identify foreign proteins before committing to a course of action. Will the immune system choose to protect or destroy a tissue bearing foreign proteins such as transplant? An ideal treatment for patients with type 1 diabetes mellitus is to induce T cells to protect rather then destroy an islet transplant. This would allow the transplant to function in a state of immune tolerance without use of immunosuppressive drugs. A major barrier precluding utilization of such strategies in the clinic is the lack of understanding as to how T cells can be coaxed into attacking or protecting transplants. Under adverse conditions of inflammation, T cells that normally protect islet transplant change their behavior and attack the islets. Why?

We have developed a powerful and totally unique system to image the T cell response to islet allografts in vivo enabling us to distinguish natural Tregs from induce Tregs, and both of these from T effector in longitudinal studies using minimally invasive in vivo imaging and relate these data to the clinical status of the allograft in conditions of rejection versus tolerance. We will now determine the impact of tolerance blocking inflammatory stimuli upon natural and induced Tregs and the induction/maintenance of islet transplant tolerance using our unique set of tools. Using a powerful new imaging system we can now address and resolve this vexing issue.

Research Profile

What area of diabetes research does your project cover? What role will this particular project play in preventing, treating, and curing diabetes?

My research focus for the last 30 years is to find a cure for Type 1 diabetes and recently Type 2. Immune cells take cues from the environment in which they identify foreign proteins before committing to a course of action. Will the immune system choose to protect or destroy a tissue bearing foreign proteins such as transplant? An ideal treatment for patients with Type 1 diabetes is to induce T cells to protect rather than destroy an islet transplant. This would allow the transplant to function in a state of immune tolerance without use of immunosuppressive drugs.

A major barrier precluding utilization of such strategies in the clinic is the lack of understanding as to how T cells can be coaxed into attacking or protecting transplants. Under adverse conditions of inflammation, T cells that normally protect islet transplant change their behavior and attack the islets. Why? We have developed a powerful and totally unique system to image the T cell response to islet allografts in vivo, enabling us to distinguish natural Tregs from induce Tregs, and both of these from T effector in longitudinal studies using minimally invasive in vivo imaging and relate these data to the clinical status of the allograft in conditions of rejection versus tolerance.

We will now determine the impact of tolerance blocking inflammatory stimuli upon natural and induced Tregs and the induction/maintenance of islet transplant tolerance using our unique set of tools. Using a powerful new imaging system we can now address and resolve this vexing issue.

If a person with diabetes were to ask you how your project will help them in the future, how would you respond?

In time this research can help every patient in need of islet cell transplantation.

A similar circumstance related to the curative effects of a variety of therapies that successfully restore euglycemia in Type 1 and Type 2 diabetic patients. We are establishing a road map to the cure.

We believe that we are on the right track  in our efforts to produce tolerance and a means to overcome the unacceptable non-immunologic loss of transplanted islets in the clinic and reverse diabetes.

Why is it important for you, personally, to become involved in diabetes research? What role will this award play in your efforts?

I have devoted my whole research career in finding a cure for diabetes.  Over 30 years of my research has been focused on developing new treatments for diabetes.

I have developed and tested new therapeutics in both mouse diabetes and monkey islet transplant models. Two of my regimens have proven so successful that they will be introduced into human clinical trials as test therapies for individuals with new onset Type 1 diabetes. One of them (alpha1 anti-trypsin) is in clinical trails for Type 1 diabetes.

Our new research award will help us in understandings how to control  the destructive inflammation as well as T-cell immunity which are the keys to curing Type I  diabetes or in recipients of organ transplants.

In time this research can help every patient with both Type 1 and 2 diabetes as well as patients in need of islet cell transplantation.

In what direction do you see the future of diabetes research going?

The direction of the future of diabetes research would include novel therapeutic treatments that successfully restore euglycemia in Type 1 and Type 2 diabetic patients. Treatments should not only reverse diabetes but also insulin resistance and induce tolerance in islet transplantation.